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P.2.e.015 Clinical trials to clinical practice: retrospective analysis of 25 patients with bipolar mania treated with aripiprazole
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P.2.e. Affective disorders and antidepressants − Bipolar disorders (clinical)
quetiapine+sertraline had a depression recurrence at week30 that require dosage adjustment of both drugs and continued the study, and one male treated with quetiapine+fluoxetine had a mania recurrence at week38 and dropped out because of psychiatric hospitalization; therefore of baseline 44 subjects 41 (22 females) were evaluated up to week54, mean age 42.0±5.4; twenty-one were treated with AD (fluoxetine n = 5 26.0±5.5 mg/day, sertraline n = 6 75.0±22.3 mg/day, duloxetine n = 10 81.0±28.5 mg/day) and dosage of quetiapine was not different in the two groups (with vs without AD, 573.1±144.8 vs 568.5±107.8 mg/day). The efficacy over depressive symptoms progressed over time but parallel in both groups; respectively group without AD vs AD-treated, HAMD-21 week18 scores dropped from 19.2±6.0 vs 19.1±7.2 to 10.7±4.0 vs 9.4±3.9: ANOVA repeated measures: time effect (two levels: week18 and week54) p < 0.001, treatment (without or with AD) p = 0.61; interaction timeXtreatment p = 0.57; relatively to YMRS scores, on the contrary a similar continued improvement until study end was observed but with differences in two groups, week18 scores dropped from 16.5±4.7 vs 9.6±3.8 to week54 score 10.2±3.1 vs 6.1±2.3: repeatedmeasures ANOVA revealed significant time effect p < 0.001, treatment p < 0.005; and interaction p = 0.001. Three YMRS item scores improved significantly: irritability, disruptive aggressive behaviour and insomnia. In the entire sample in the whole period of study no suicide attempters were revealed, as assessed by a score of 4 at suicide HAMD item. Conclusion: We cautiously suggest that adding an AD in order to treat every main features of mixed episode further improved the outcome. Moreover, in the long term, continuing the AD treatment further improve symptomatology, as indicated by a significant reduction of both HAMD-21 and YMRS scores; unexpectedly, the aspects better controlled seemed to be the manic ones, particularly disruptive aggressive behavior, irritability and insomnia. References [1] G. Callista, E. Daneluzzo. Combined antidepressant and quetiapine therapy in bipolar I mixed − an open label study. European Neuropsychopharmacology 2008 volume 18 Supplement 4 p.364. [2] G. Callista, E. Daneluzzo Effects of duloxetine adjunctive to extendedrelease quetiapine treatment in bipolar I mixed − an open label study. International Journal of Psychiatry in Clinical Practice volume 13 Supplement 1 November 2009 pp. 25−26. [3] G. Callista, E. Daneluzzo Combined antidepressant and quetiapine therapy in bipolar I mixed. European Psychiatry Abstract Vol. 25 Suppl. 1 2010 P01−18.
P.2.e.015 Clinical trials to clinical practice: retrospective analysis of 25 patients with bipolar mania treated with aripiprazole T. Rana1 ° . 1 Park House, Psychiatry Department, Cannock, United Kingdom Background: Aripiprazole is an established agent for the management of schizophrenia. More recently, it has been approved in Europe for bipolar mania, based on a rigorous clinical development programme, but there is a need for further published real-life experience, particularly with a long-term focus. Purpose: To share acute and long-term clinical experience with aripiprazole in patients with bipolar mania who were referred to a single centre or hospitalised, with follow-up of >12 months. Methods: 25 consecutive patients (April–December 2008) with a diagnosis of bipolar disorder (ICD-10) presenting with manic
symptoms and for whom an atypical antipsychotic was appropriate were prescribed aripiprazole and managed according to standard centre protocols. Community patients were reassessed every 4−6 weeks and in-patients daily. Response was based on clinical observation of a reduction in core symptoms and subjective reporting by patients substantiated by carers. Case data were analysed retrospectively when all patients had been followed for at least 12 months. Table 1. Patient demographics Gender Male Female Age Time since diagnosis Status
Comorbidities Personality disorder Substance misuse Eating disorder Epilepsy Presenting manic episode With psychotic symptoms Without psychotic symptoms Setting In-patient Community Antipsychotic use (presentation) Olanzapine, 20 mg OD Quetiapine, 600–800 mg OD Risperidone, 6 mg OD Haloperidol, 100 mg every 4 weeks Flupentixol, 150 mg every 4 weeks
9 (36%) 16 (64%) 20−63 years 4 weeks to 40 years 16 (64%) married 11 (44%) employed 7 (28%) living alone 18 (72%) had carers 4 2 1 1 6 (24%) 19 (76%) 6 (24%) 19 (76%) 11 5 2 1 1
Results: Demographics are shown in Table 1. Duration of follow-up was 13−21 months. Five patients were antipsychoticna¨ıve and 20 switched to aripiprazole from another antipsychotic. Reasons for switching were weight gain, excessive sedation and sexual dysfunction, alone or in combination. In switch patients, aripiprazole was initiated at 15 mg, the previous antipsychotic was tapered off over 3−4 weeks and then aripiprazole was increased if necessary. Benzodiazepines were used in the short term if required (n = 18). Final stable aripiprazole doses were 15 mg (nine patients), 20 mg (eight patients), 25 mg (five patients) and 30 mg (three patients). Manic symptoms resolved completely in 24 patients; the remaining individual had a partial response and required additional haloperidol. Response was seen from as early as Day 2 and within 1 week in 60% of cases. Six patients developed depressive symptoms that were managed with an antidepressant with continued aripiprazole. Restlessness and agitation were reported by four patients; headache was reported by two individuals. These possible side-effects did not require dose modification. There were no discontinuations. Importantly, all 25 patients were able to resume their day-to-day functioning and those who were employed returned to work. Five in-patients were discharged from hospital, after 4−6 weeks, and the remaining patient was discharged to a secure unit. During follow-up, there were no relapses. No patients or their doctors reported any worsening of physical health.
P.2.e. Affective disorders and antidepressants − Bipolar disorders (clinical) Conclusions: Real-life experience with aripiprazole demonstrates it provides rapid control of manic symptoms in the acute phase and prevents relapse in the long-term. Slow tapering can be an effective switch strategy for in-patient and community settings. Disclosure statement: This paper is financially supported by an unrestricted educational grant from Bristol-Myers Squibb UK Ltd and Otsuka Pharmaceutical UK Ltd P.2.e.016 Psychotic versus non-psychotic bipolar II disorder A. Murru1 ° , L. Mazzarini1 , F. Colom1 , I. Pacchiarotti1 , A.M.A. Nivoli1 , C.M. Bonnin1 , G.D. Kotzalidis1 , E. Vieta1 . 1 IDIBAPS-CIBERSAM Hospital Clinic, Bipolar Disorder Program, Barcelona, Spain Introduction: Psychotic symptoms in bipolar II disorder, allowed by definition only during a depressive episode, are present in a range between 3% and 45%. Little is known regarding the impact of psychotic symptoms on the clinical course of bipolar II patients. Findings from previous reports are controversial and focused specifically on bipolar I disorder. Only a few studies have been conducted on samples composed exclusively of bipolar II patients. The aim of this study was to ascertain the clinical characteristics of individuals with bipolar II disorder with and without lifetime history of psychotic symptoms. To our knowledge, there is no published research that focuses specifically on the impact of lifetime history of psychotic symptoms on the clinical course of bipolar II patients by comparing bipolar II patients with and without a history of psychosis. Methods: The sample consisted of 164 DSM-IV [1] Bipolar II patients consecutively recruited from the Barcelona Bipolar Disorder Program. Patients were divided in Bipolar II patients with (N = 32) and without (N = 132) lifetime history of psychotic symptoms. Clinical and socio-demographic features were compared. Both groups were compared regarding sociodemographic and clinical variables. First, we ran one-way ANOVA (F-test) for quantitative variables. We then used Pearson’s chi square test (c2 ) to analyze the categorical variables. We set the alpha level for statistical significance at p < 0.05. Results: Thirty-two out of 164 patients with bipolar II disorder had a history of psychosis during depression (19.5%). Bipolar II patients with a history of psychotic symptoms showed a higher number of hospitalizations than patients without such a history (p < 0.001). They were also older but were less likely to have a family history of bipolar illness and any mental disorder than nonpsychotic bipolar II patients. Melancholic and catatonic features were significantly more frequent in psychotic bipolar II patients (p < 0.001). No statistical difference in demographic, occupational functioning and clinical data such as gender age of onset, number of hypomanic and depressive episodes, type of first episode, axis I and II comorbidity, seasonality, rapid cycling and suicide attempts were found. Conclusions: Our findings confirm that the presence of psychotic symptoms in bipolar II disorder, which by definition can occur exclusively in the depressive phase, is not rare. Our data indicate that bipolar II disorder with a history of psychotic symptoms was less severe than bipolar II disorder without psychotic symptoms with regard to episode frequency, but was more severe with respect to symptom intensity. Psychotic bipolar II disorder may be a different phenotype from non-psychotic bipolar disorder. Neurocognition in psychotic and non-psychotic bipolar disorder should be examined separately, because studying collective
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bipolar diagnostic groups may obscure potential findings. Future investigations using quantitative indices of psychosis-proneness could help better assessing the presence and understanding the relationship of subtle or subthreshold psychotic symptoms to bipolar disorder. References [1] American Psychiatric Association. 1994. Diagnostic and Statistical Manual of Mental Disorders DSM-IV. 4th ed. Washington, DC.
P.2.e.017 Life-time suicide attempts in acutely admitted inpatients with bipolar disorder P.I. Finseth1 ° , G. Morken1 , U.F. Malt2 , O.A. Andreassen3 , 1 Department of neuroscience/Division of A.E. Vaaler1 . psychiatry, Faculty of medicine NTNU/St Olavs Hospital, Trondheim, Norway; 2 Insitute of psychiatry/Department of Neuropsychiatry and Psychosomatic Medicine, Faculty of medicine University of Oslo/Oslo University Hospital, Oslo, Norway; 3 Insitute of psychiatry/Department of psychiatry, Faculty of medicine University of Oslo/Oslo University Hospital, Oslo, Norway Purpose of the study: To compare acutely admitted bipolar inpatients with and without life-time suicide attempts, including dominant polarity of illness, frequency of psychotic episodes and reactions to antidepressants. Methods: All bipolar I and II patients admitted to the acute ward of the Østmarka Department of Psychiatry, St. Olavs University Hospital, Trondheim, Norway, between November 2002 and July 2009 were included in this study. All patients in the catchment area are admitted to this hospital. Diagnoses were verified by SCID 1. Patients with a history of a serious suicide attempt were compared with patients without. A serious suicide attempt was defined as one requiring medical attention, emergency room visit or hospitalization. Results: 206 consecutive patients were included. Of them there were 113 women (55%) and 93 (45%) men. 136 patients (66%) had bipolar I and 70 patients (34%) bipolar II disorder. 93 patients (45%) had a life-time history of one or more suicide attempts. No sociodemographic discrepancies were shown, nor for bipolar subtype. Clinical features at inclusion and historical course of illness are presented in Table 1. Table 1. Life-time suicide attempts in acutely admitted inpatients with bipolar disorder Non-attempters Attempters p (N = 113) (N = 93) Men Women* Bipolar I (N, %)* Age in years±SD** Duration of illness in years ±SD** No. of hospitalizations, total, median (min-max)*** No. of depressive episodes, median (min-max)*** No. of hospitalizations due to depression, median (min-max)*** No. of hypomanic and or manic episodes, median (min-max)*** No. of hospitalizations due to mania, median (min-max)*** Index admission depression (N, %)* Mania or hypomania induced by antidepressant (N, %)* Increasing severity of affective episodes (N, %)* Rapid cycling (N, %)* Psychotic diagnosis, lifetime (N, %)*
56/93 57/113 79, 70% 41±15 21±16 2 (0−31) 5 (0−51) 1 (0−10) 5.5 (0–100) 1 (0−30) 45, 43% 7, 6% 54, 51% 13, 12% 61, 54%
37/93 56/113 57, 61% 44±14 24±14 2 (0−30) 8 (1−51) 2 (0−20) 5 (0−51) 0 (0−20) 55, 62% 14, 16% 58, 64% 19, 21% 35, 38%
ns ns ns ns ns 0.042 <0.000 ns 0.004 0.007 0.033 0.060 0.077 0.019
*Chi Square test; **Student’s t-test; ***Mann Whitney test.
Conclusions: A life-time suicide attempt rate of 45% is within the upper range of previous reports [1]. Few earlier studies have included only inpatients. Attempters had a dominant depressive
P.2.e. Affective disorders and antidepressants − Bipolar disorders (clinical)
quetiapine+sertraline had a depression recurrence at week30 that require dosage adjustment of both drugs and continued the study, and one male treated with quetiapine+fluoxetine had a mania recurrence at week38 and dropped out because of psychiatric hospitalization; therefore of baseline 44 subjects 41 (22 females) were evaluated up to week54, mean age 42.0±5.4; twenty-one were treated with AD (fluoxetine n = 5 26.0±5.5 mg/day, sertraline n = 6 75.0±22.3 mg/day, duloxetine n = 10 81.0±28.5 mg/day) and dosage of quetiapine was not different in the two groups (with vs without AD, 573.1±144.8 vs 568.5±107.8 mg/day). The efficacy over depressive symptoms progressed over time but parallel in both groups; respectively group without AD vs AD-treated, HAMD-21 week18 scores dropped from 19.2±6.0 vs 19.1±7.2 to 10.7±4.0 vs 9.4±3.9: ANOVA repeated measures: time effect (two levels: week18 and week54) p < 0.001, treatment (without or with AD) p = 0.61; interaction timeXtreatment p = 0.57; relatively to YMRS scores, on the contrary a similar continued improvement until study end was observed but with differences in two groups, week18 scores dropped from 16.5±4.7 vs 9.6±3.8 to week54 score 10.2±3.1 vs 6.1±2.3: repeatedmeasures ANOVA revealed significant time effect p < 0.001, treatment p < 0.005; and interaction p = 0.001. Three YMRS item scores improved significantly: irritability, disruptive aggressive behaviour and insomnia. In the entire sample in the whole period of study no suicide attempters were revealed, as assessed by a score of 4 at suicide HAMD item. Conclusion: We cautiously suggest that adding an AD in order to treat every main features of mixed episode further improved the outcome. Moreover, in the long term, continuing the AD treatment further improve symptomatology, as indicated by a significant reduction of both HAMD-21 and YMRS scores; unexpectedly, the aspects better controlled seemed to be the manic ones, particularly disruptive aggressive behavior, irritability and insomnia. References [1] G. Callista, E. Daneluzzo. Combined antidepressant and quetiapine therapy in bipolar I mixed − an open label study. European Neuropsychopharmacology 2008 volume 18 Supplement 4 p.364. [2] G. Callista, E. Daneluzzo Effects of duloxetine adjunctive to extendedrelease quetiapine treatment in bipolar I mixed − an open label study. International Journal of Psychiatry in Clinical Practice volume 13 Supplement 1 November 2009 pp. 25−26. [3] G. Callista, E. Daneluzzo Combined antidepressant and quetiapine therapy in bipolar I mixed. European Psychiatry Abstract Vol. 25 Suppl. 1 2010 P01−18.
P.2.e.015 Clinical trials to clinical practice: retrospective analysis of 25 patients with bipolar mania treated with aripiprazole T. Rana1 ° . 1 Park House, Psychiatry Department, Cannock, United Kingdom Background: Aripiprazole is an established agent for the management of schizophrenia. More recently, it has been approved in Europe for bipolar mania, based on a rigorous clinical development programme, but there is a need for further published real-life experience, particularly with a long-term focus. Purpose: To share acute and long-term clinical experience with aripiprazole in patients with bipolar mania who were referred to a single centre or hospitalised, with follow-up of >12 months. Methods: 25 consecutive patients (April–December 2008) with a diagnosis of bipolar disorder (ICD-10) presenting with manic
symptoms and for whom an atypical antipsychotic was appropriate were prescribed aripiprazole and managed according to standard centre protocols. Community patients were reassessed every 4−6 weeks and in-patients daily. Response was based on clinical observation of a reduction in core symptoms and subjective reporting by patients substantiated by carers. Case data were analysed retrospectively when all patients had been followed for at least 12 months. Table 1. Patient demographics Gender Male Female Age Time since diagnosis Status
Comorbidities Personality disorder Substance misuse Eating disorder Epilepsy Presenting manic episode With psychotic symptoms Without psychotic symptoms Setting In-patient Community Antipsychotic use (presentation) Olanzapine, 20 mg OD Quetiapine, 600–800 mg OD Risperidone, 6 mg OD Haloperidol, 100 mg every 4 weeks Flupentixol, 150 mg every 4 weeks
9 (36%) 16 (64%) 20−63 years 4 weeks to 40 years 16 (64%) married 11 (44%) employed 7 (28%) living alone 18 (72%) had carers 4 2 1 1 6 (24%) 19 (76%) 6 (24%) 19 (76%) 11 5 2 1 1
Results: Demographics are shown in Table 1. Duration of follow-up was 13−21 months. Five patients were antipsychoticna¨ıve and 20 switched to aripiprazole from another antipsychotic. Reasons for switching were weight gain, excessive sedation and sexual dysfunction, alone or in combination. In switch patients, aripiprazole was initiated at 15 mg, the previous antipsychotic was tapered off over 3−4 weeks and then aripiprazole was increased if necessary. Benzodiazepines were used in the short term if required (n = 18). Final stable aripiprazole doses were 15 mg (nine patients), 20 mg (eight patients), 25 mg (five patients) and 30 mg (three patients). Manic symptoms resolved completely in 24 patients; the remaining individual had a partial response and required additional haloperidol. Response was seen from as early as Day 2 and within 1 week in 60% of cases. Six patients developed depressive symptoms that were managed with an antidepressant with continued aripiprazole. Restlessness and agitation were reported by four patients; headache was reported by two individuals. These possible side-effects did not require dose modification. There were no discontinuations. Importantly, all 25 patients were able to resume their day-to-day functioning and those who were employed returned to work. Five in-patients were discharged from hospital, after 4−6 weeks, and the remaining patient was discharged to a secure unit. During follow-up, there were no relapses. No patients or their doctors reported any worsening of physical health.
P.2.e. Affective disorders and antidepressants − Bipolar disorders (clinical) Conclusions: Real-life experience with aripiprazole demonstrates it provides rapid control of manic symptoms in the acute phase and prevents relapse in the long-term. Slow tapering can be an effective switch strategy for in-patient and community settings. Disclosure statement: This paper is financially supported by an unrestricted educational grant from Bristol-Myers Squibb UK Ltd and Otsuka Pharmaceutical UK Ltd P.2.e.016 Psychotic versus non-psychotic bipolar II disorder A. Murru1 ° , L. Mazzarini1 , F. Colom1 , I. Pacchiarotti1 , A.M.A. Nivoli1 , C.M. Bonnin1 , G.D. Kotzalidis1 , E. Vieta1 . 1 IDIBAPS-CIBERSAM Hospital Clinic, Bipolar Disorder Program, Barcelona, Spain Introduction: Psychotic symptoms in bipolar II disorder, allowed by definition only during a depressive episode, are present in a range between 3% and 45%. Little is known regarding the impact of psychotic symptoms on the clinical course of bipolar II patients. Findings from previous reports are controversial and focused specifically on bipolar I disorder. Only a few studies have been conducted on samples composed exclusively of bipolar II patients. The aim of this study was to ascertain the clinical characteristics of individuals with bipolar II disorder with and without lifetime history of psychotic symptoms. To our knowledge, there is no published research that focuses specifically on the impact of lifetime history of psychotic symptoms on the clinical course of bipolar II patients by comparing bipolar II patients with and without a history of psychosis. Methods: The sample consisted of 164 DSM-IV [1] Bipolar II patients consecutively recruited from the Barcelona Bipolar Disorder Program. Patients were divided in Bipolar II patients with (N = 32) and without (N = 132) lifetime history of psychotic symptoms. Clinical and socio-demographic features were compared. Both groups were compared regarding sociodemographic and clinical variables. First, we ran one-way ANOVA (F-test) for quantitative variables. We then used Pearson’s chi square test (c2 ) to analyze the categorical variables. We set the alpha level for statistical significance at p < 0.05. Results: Thirty-two out of 164 patients with bipolar II disorder had a history of psychosis during depression (19.5%). Bipolar II patients with a history of psychotic symptoms showed a higher number of hospitalizations than patients without such a history (p < 0.001). They were also older but were less likely to have a family history of bipolar illness and any mental disorder than nonpsychotic bipolar II patients. Melancholic and catatonic features were significantly more frequent in psychotic bipolar II patients (p < 0.001). No statistical difference in demographic, occupational functioning and clinical data such as gender age of onset, number of hypomanic and depressive episodes, type of first episode, axis I and II comorbidity, seasonality, rapid cycling and suicide attempts were found. Conclusions: Our findings confirm that the presence of psychotic symptoms in bipolar II disorder, which by definition can occur exclusively in the depressive phase, is not rare. Our data indicate that bipolar II disorder with a history of psychotic symptoms was less severe than bipolar II disorder without psychotic symptoms with regard to episode frequency, but was more severe with respect to symptom intensity. Psychotic bipolar II disorder may be a different phenotype from non-psychotic bipolar disorder. Neurocognition in psychotic and non-psychotic bipolar disorder should be examined separately, because studying collective
S411
bipolar diagnostic groups may obscure potential findings. Future investigations using quantitative indices of psychosis-proneness could help better assessing the presence and understanding the relationship of subtle or subthreshold psychotic symptoms to bipolar disorder. References [1] American Psychiatric Association. 1994. Diagnostic and Statistical Manual of Mental Disorders DSM-IV. 4th ed. Washington, DC.
P.2.e.017 Life-time suicide attempts in acutely admitted inpatients with bipolar disorder P.I. Finseth1 ° , G. Morken1 , U.F. Malt2 , O.A. Andreassen3 , 1 Department of neuroscience/Division of A.E. Vaaler1 . psychiatry, Faculty of medicine NTNU/St Olavs Hospital, Trondheim, Norway; 2 Insitute of psychiatry/Department of Neuropsychiatry and Psychosomatic Medicine, Faculty of medicine University of Oslo/Oslo University Hospital, Oslo, Norway; 3 Insitute of psychiatry/Department of psychiatry, Faculty of medicine University of Oslo/Oslo University Hospital, Oslo, Norway Purpose of the study: To compare acutely admitted bipolar inpatients with and without life-time suicide attempts, including dominant polarity of illness, frequency of psychotic episodes and reactions to antidepressants. Methods: All bipolar I and II patients admitted to the acute ward of the Østmarka Department of Psychiatry, St. Olavs University Hospital, Trondheim, Norway, between November 2002 and July 2009 were included in this study. All patients in the catchment area are admitted to this hospital. Diagnoses were verified by SCID 1. Patients with a history of a serious suicide attempt were compared with patients without. A serious suicide attempt was defined as one requiring medical attention, emergency room visit or hospitalization. Results: 206 consecutive patients were included. Of them there were 113 women (55%) and 93 (45%) men. 136 patients (66%) had bipolar I and 70 patients (34%) bipolar II disorder. 93 patients (45%) had a life-time history of one or more suicide attempts. No sociodemographic discrepancies were shown, nor for bipolar subtype. Clinical features at inclusion and historical course of illness are presented in Table 1. Table 1. Life-time suicide attempts in acutely admitted inpatients with bipolar disorder Non-attempters Attempters p (N = 113) (N = 93) Men Women* Bipolar I (N, %)* Age in years±SD** Duration of illness in years ±SD** No. of hospitalizations, total, median (min-max)*** No. of depressive episodes, median (min-max)*** No. of hospitalizations due to depression, median (min-max)*** No. of hypomanic and or manic episodes, median (min-max)*** No. of hospitalizations due to mania, median (min-max)*** Index admission depression (N, %)* Mania or hypomania induced by antidepressant (N, %)* Increasing severity of affective episodes (N, %)* Rapid cycling (N, %)* Psychotic diagnosis, lifetime (N, %)*
56/93 57/113 79, 70% 41±15 21±16 2 (0−31) 5 (0−51) 1 (0−10) 5.5 (0–100) 1 (0−30) 45, 43% 7, 6% 54, 51% 13, 12% 61, 54%
37/93 56/113 57, 61% 44±14 24±14 2 (0−30) 8 (1−51) 2 (0−20) 5 (0−51) 0 (0−20) 55, 62% 14, 16% 58, 64% 19, 21% 35, 38%
ns ns ns ns ns 0.042 <0.000 ns 0.004 0.007 0.033 0.060 0.077 0.019
*Chi Square test; **Student’s t-test; ***Mann Whitney test.
Conclusions: A life-time suicide attempt rate of 45% is within the upper range of previous reports [1]. Few earlier studies have included only inpatients. Attempters had a dominant depressive