- Email: [email protected]
Social cognition deficits in bipolar disorder – associations with overweight and obesity
S438
P.2.d. Mood disorders and treatment − Bipolar disorders (clinical)
intensity (p < 10−3 ), emotional polarity (p = 0.034) and emotional stability (p = 0.006). In addition to the difference with control subjects, patients differed from their first-degree relatives and had higher scores for the total score (p = 0.001), and the scores of three dimensions: emotional intensity (p = 0.007), emotional intensity (p < 10−3 ) and emotional stability (p = 0.008). However, we did not find a difference between the first-degree relatives of bipolar patients and the control group (p = 0.92). Conclusion: In our study, normothymic bipolar patients showed an emotional hyperreactivity compared to their first-degree relatives and the control group. This emotional hyperreactivity seems to characterize patients and not their relatives which does not confirm the hypothesis of considering it as an endophenotype of the disease.
P.2.d.032 Hyponatremia in bipolar disorder treated with oxcarbazepine: report of a case
performing MRI compatible lesions are observed with central pontine myelinolysis. As the definitive diagnosis. Diagnostic formulation: – Axis I; Bipolar Disorder – Axis II; unidentified – Axis III; Central pontine myelinolysis – Axis IV; Problems related to the work environment – Axis V; GAP = 60. Conclusions: The patient has an acute onset with a history of hospitalization with severe hyponatremia secondary to oxcarbazepine, which was corrected abruptly. The presentation of the table and MRI make us suspect the presence of an organic substrate as the cause of these symptoms and not secondary to psychiatric disorders. Between 40% and 60% of organic pathology it is obviated in receptions of patients in the ER and thus lose precious time for proper treatment. We must be alert to this type of organic disorders masked psychiatric symptoms that cause incorrect treatment.
1 Hosp.
M.E. Ortigosa Luque1 , M. Valverde Barea2 ° , F. Cartas Moreno2 Princesa de Espa˜na, Jaen, Spain; 2 Hosp. Princesa de Espa˜na, psychiatry, Jaen, Spain
P.2.d.033 Social cognition deficits in bipolar disorder − associations with overweight and obesity
Summary: Delirium is a multi-etiological clinical syndrome whose essential feature is the alteration of consciousness that is accompanied by a change especially at attention and alert. It accompanied by a change in cognition broadly representative; Memory, perception, abstraction, reasoning, emotion and executive functions of planning, task sequencing, resistance to interference and perseverance. It may be secondary to substance, a medical condition or have unspecified origin. Let’s look at a case in which psychiatrists must give a differential diagnosis of an acute confusional state remains the fundamental objective to differentiate psychiatric disorders of purely organic tables presenting symptoms that can overlap. Making the case: 51 year old patient with a history of hypothyroidism, chronic alcohol abuse, Bipolar disorder treated with oxcarbazepine 600 mg every 12 h and olanzapine 10 mg comp 1 every 24 hours. The patient is admitted to the hospital with severe hyponatremia (Less than 125 meqv / l). During her stay in the hospital she recovered quickly from hyponatremia and she was discharged after five days of admission, she was diagnosed with severe hyponatremia secondary to oxcarbazepine. At discharge the patient goes with the next treatment; Olanzapine 10 mg comp 1 every 24 hours, valproic Ac 500 mg comp 1 every 12 h. The patient is transferred to his home and at 7 days begins to suffer episodes of disorientation, confusion, psychomotor agitation, speech disorder, clumsiness in ambulation. She is seen by the internist guard, to explore, only a partial disorientation is detected in time but not in space, with normal gait and the rest of the neurological examination within normal limits. The diagnostic impression was a psychiatric disorders and alternately encephalopathy of unknown origin. Following a cranial computed axial tomography in which nothing is detected Psychiatry valuation is decided. The patient is admitted to Psychiatry and after several diagnostic tests are performed differential diagnosis; Dementia, depression or confused Mania Phase of Bipolar disorder, dissociative disorder, disorders resulting from alcohol consumption. During admission psychomotor restlessness recedes but continuous clouded, and gait disturbances are increasing appear. After
N. Lackner1 ° , A. Birner1 , S.A. Bengesser1 , F.T. Fellendorf1 , M. Platzer1 , R. Queissner1 , H.P. Kapfhammer1 , B. Reininghaus2 , E. Weiss3 , S.J. Wallner-Liebmann4 , E.Z. Reininghaus1 1 Medical University of Graz, Psychiatry, Graz, Austria; 2 Therapiezentrum Justuspark, Bva, Bad Hall, Austria; 3 Karl-Franzens University Graz, Biological Psychology, Graz, Austria; 4 Medical University of Graz, Pathophysiology and Immunology, Graz, Austria Introduction: Bipolar affective disorder has consequently related to overweight and obesity [1,2] as well as metabolic abnormalities [3]. Previous research also has suggested that cognitive deficits are associated with overweight and obesity in bipolar disorder [4]. In addition, impairments in social cognition so called Theory of Mind deficits are well established in bipolar disorder. Affect recognition abilites are related negative to clinical course of psychiatric patients [5]. Consequently, overweight and obesity have been associated with a worse course and psychiatric symptoms in bipolar disorder [2]. In the present study, we wanted to test the hypothesis that impaired Theory of Mind functions are associated with measures of overweight and obesity in a well characterized sample of euthymic individuals with bipolar disorder. Method: A group of 116 patients with bipolar affective disorder treated at the psychiatric outpatient-centre for bipolar affective disorder of the Medical University Graz was investigated with a social cognition task to measure facial affect recognition (the Reading the Mind in the Eyes (RMET)), and an anthropometric measurement set (Body mass index, Waist-to-Hip-Ratio, Weightto-Height-Ratio). Patients were diagnosed according to DSM-IV, and 38 patients additionally met criteria for the harmful metabolic syndrome (defined as a cluster of clinical and biochemical risk factors for cardiovascular disease and type 2 diabetes mellitus). In addition, a healthy control group (n = 83) was investigated using the same methods. Group differences were assessed with analyses of variance. To test associations between RMET performance and anthropometric measures, Pearson correlation coefficients were used. Results: Overall, our findings demonstrate an impaired performance on the RMET in patients with bipolar disorder compared with controls (F = 7.88, p < 0.01). The results suggest a negative
P.2.d. Mood disorders and treatment − Bipolar disorders (clinical) correlation between performance on the RMET and Waist-to-HipRatio in the bipolar Group(r = 0.23, p < 0.05). In addition, bipolar patients with metabolic syndrome had a worse performance in RMET than patients without metabolic Syndrome F = 3.22, p < 0.05). Conclusions: To the best of our knowledge, this is the first study that measured the relationship of overweight/obesity with social cognition function in bipolar disorder. In accordance with well-known cognitive deficits in bipolar disorder, also social cognition is impaired in this patient group, even in euthymia. Consequently, there is also a relationship between overweight/obesity and facial affects recognition in bipolar disorder. The current study has also some limitations: First, there was a higher prevalence of overweight and obesity in the patient sample. Second, the patients were on psychotropic medication and the effect of these treatments were unclear. Third, the cross-sectional design of this study does not allow for direct causal conclusions regarding the association beetwen overweight/obesity and social cognition deficits in bipolar disorder. More research is needed to investigate whether social cognition treatments reduce the risk for the development and maintenance of obesity in bipolar affective disorder. References [1] McElroy, S.L., Keck Jr, P.E., 2012. Obesity in bipolar disorder: an overview. Current Psychiatry Reports, 14(6), 650–658. [2] Lackner, N., Mangge, H., Reininghaus, E.Z., McIntyre, R.S., Bengesser, S.A., Birner, A., . . . Wallner-Liebmann, S.J., 2015. Body fat distribution and associations with metabolic and clinical characteristics in bipolar individuals. European archives of psychiatry and clinical neuroscience, 265(4), 313–319. [3] Vancampfort, D., Vansteelandt, K., Correll, C.U., Mitchell, A.J., De Herdt, A., Sienaert, P., . . . De Hert, M., 2013. Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators. American Journal of Psychiatry. [4] Lackner, N., Bengesser, S.A., Birner, A., Painold, A., Fellendorf, F.T., Platzer, M., . . . Fuchs, D. 2015. Abdominal obesity is associated with impaired cognitive function in euthymic bipolar individuals. The World Journal of Biological Psychiatry, 1−12. [5] Chen, Y., Cataldo, A., Norton, D.J., Ongur, D. 2012. Distinct facial processing in schizophrenia and schizoaffective disorders. Schizophrenia Research, 134(1), 95–100.
S439
is highly tolerated and shows lower rates of the side effects typically observed with other antipsychotic drugs, including sedation, weight gain, hyperprolactinemia, and extrapyramidal syndrome. Aim: To explore the efficacy, tolerability and safety of the combined approach with aripiprazole and natrium valproate in bipolar mania. Method: Eight patients participated in this observation. Inclusion criteria were a diagnosis of BAD with manic features, with or without psychotic features according to ICD-10. Patients were treated with the combination of natrium valproate and aripiprazole. At the 8 week follow-up patients were being treated with mean doses of aripiprazole (range 15−30 mg/day) and natrium valproate (range 1200–1800 mg/day). Every patient in this group had previously been unsuccessfully treated with one typical or atypical antipsychotic drugs as combination therapy with mood stabilizers. Clinical status was evaluated at baseline and at the 4 week and 8 week, follow-up using the total Young Mania Rating Scale (YMRS), Clinical Global Impressions Bipolar (CGI-BP) mania scale. Follow-up evaluations, using the same rating scale as at baseline, were undertaken 4 week and 8 week, from the start date of aripiprazole. Results: All patients (5 women and 3 men) aged between 23 and 45 years, completed 8 week of combination treatment. The results obtained indicate that aripiprazole added to natrium valproate treatment showed a beneficial effect on the general psychopathological symptomatology in a sample of BAD patients. The YMRS total score decreased significantly from baseline to 4 week and 8 week follow-up (p < 0.05). Significant improvements were also noted on the CGI-BP scores. Conclusion: Aripiprazole and natrium valproate combination is an effective and well-tolerated option in acute mania of BAD with therapeutic benefit for patients who are partially responsive to other drugs combinations. Natrium valproate /aripiprazole combination provides greater improvement in mania, and it appears to be safe with a lower risk of metabolic syndrome, without increased risk of adverse effects, compared with other medications combination. References
P.2.d.034 The combined approach with aripiprazole and natrium valproate in bipolar mania S. Bise1 ° , G. Sulejmanpaˇsi´c2 1 Psychiatric hospital Sarajevo, women, Sarajevo, Bosnia and Herzegovina; 2 University of Sarajevo Clinical Center- Psychiatric clinic, clinical, Sarajevo, Bosnia and Herzegovina Background: Bipolar afective disorder (BAD) is a chronic illness that is characterized by recurrent episodes of mania, depression or mixed symptoms. BAD has a prevalence of approximately 2−4% in the general population and is associated with a substantial rates of recurrence, interepisodic dysfunction, comorbidity, and premature mortality. Mania is one of the most difficult to treat manifestations of BAD and antipsychotic drugs play a major therapeutic role in this respect. Patients with BAD require combined therapeutic approach because of the cyclic disorder nature. Many studies report the combination of mood-stabilizing agents with atypical antipsychotics. Aripiprazole is approved for the acute management and maintenance of manic and mixed episodes associated with BD. Aripiprazole acts as a serotonin 5-HT2A receptor antagonist, as well as a partial agonist of the serotonin 5-HT1A and dopamine D2 receptors. It can be safely used, as it
[1] Vieta, E., T’joen, C., Mcquade, R.D., Carson, W.H. Jr., Marcus, R.N., Sanchez, R., Owen, R., Nameche, L., 2008. Efficacy of adjunctive aripiprazole to either valproate or lithium in bipolar mania patients partially nonresponsive to valproate/lithium monotherapy: a placebocontrolled study. American Journal of Psychiatry 165, 1316–1325. [2] Scherk, H., Pajonk, F.G., Leucht, S., 2007. Second-generation antipsychotic agents in the treatment of acute mania: a systematic review and meta-analysis of randomized controlled trials. Arch Gen Psychiatry 64, 442–455. [3] Marcus, R., Khan, A., Rollin, L., Morris, B., Timko, K., Carson, W., Sanchez, R. 2011. Efficacy of aripiprazole adjunctive to lithium or valproate in the long-term treatment of patients with bipolar I disorder with an inadequate response to lithium or valproate monotherapy: a multicenter, double-blind, randomized study. Bipolar Disorders. 13, 133–144. [4] Keck, P.E. Jr, Marcus, R., Tourkodimitris, S., Ali, M., Liebeskind, A., et al., 2003. A placebo-controlled, double-blind study of the efficacy and safety of aripiprazole in patients with acute bipolar mania. Am J Psychiatry 160, 1651–1658.
P.2.d. Mood disorders and treatment − Bipolar disorders (clinical)
intensity (p < 10−3 ), emotional polarity (p = 0.034) and emotional stability (p = 0.006). In addition to the difference with control subjects, patients differed from their first-degree relatives and had higher scores for the total score (p = 0.001), and the scores of three dimensions: emotional intensity (p = 0.007), emotional intensity (p < 10−3 ) and emotional stability (p = 0.008). However, we did not find a difference between the first-degree relatives of bipolar patients and the control group (p = 0.92). Conclusion: In our study, normothymic bipolar patients showed an emotional hyperreactivity compared to their first-degree relatives and the control group. This emotional hyperreactivity seems to characterize patients and not their relatives which does not confirm the hypothesis of considering it as an endophenotype of the disease.
P.2.d.032 Hyponatremia in bipolar disorder treated with oxcarbazepine: report of a case
performing MRI compatible lesions are observed with central pontine myelinolysis. As the definitive diagnosis. Diagnostic formulation: – Axis I; Bipolar Disorder – Axis II; unidentified – Axis III; Central pontine myelinolysis – Axis IV; Problems related to the work environment – Axis V; GAP = 60. Conclusions: The patient has an acute onset with a history of hospitalization with severe hyponatremia secondary to oxcarbazepine, which was corrected abruptly. The presentation of the table and MRI make us suspect the presence of an organic substrate as the cause of these symptoms and not secondary to psychiatric disorders. Between 40% and 60% of organic pathology it is obviated in receptions of patients in the ER and thus lose precious time for proper treatment. We must be alert to this type of organic disorders masked psychiatric symptoms that cause incorrect treatment.
1 Hosp.
M.E. Ortigosa Luque1 , M. Valverde Barea2 ° , F. Cartas Moreno2 Princesa de Espa˜na, Jaen, Spain; 2 Hosp. Princesa de Espa˜na, psychiatry, Jaen, Spain
P.2.d.033 Social cognition deficits in bipolar disorder − associations with overweight and obesity
Summary: Delirium is a multi-etiological clinical syndrome whose essential feature is the alteration of consciousness that is accompanied by a change especially at attention and alert. It accompanied by a change in cognition broadly representative; Memory, perception, abstraction, reasoning, emotion and executive functions of planning, task sequencing, resistance to interference and perseverance. It may be secondary to substance, a medical condition or have unspecified origin. Let’s look at a case in which psychiatrists must give a differential diagnosis of an acute confusional state remains the fundamental objective to differentiate psychiatric disorders of purely organic tables presenting symptoms that can overlap. Making the case: 51 year old patient with a history of hypothyroidism, chronic alcohol abuse, Bipolar disorder treated with oxcarbazepine 600 mg every 12 h and olanzapine 10 mg comp 1 every 24 hours. The patient is admitted to the hospital with severe hyponatremia (Less than 125 meqv / l). During her stay in the hospital she recovered quickly from hyponatremia and she was discharged after five days of admission, she was diagnosed with severe hyponatremia secondary to oxcarbazepine. At discharge the patient goes with the next treatment; Olanzapine 10 mg comp 1 every 24 hours, valproic Ac 500 mg comp 1 every 12 h. The patient is transferred to his home and at 7 days begins to suffer episodes of disorientation, confusion, psychomotor agitation, speech disorder, clumsiness in ambulation. She is seen by the internist guard, to explore, only a partial disorientation is detected in time but not in space, with normal gait and the rest of the neurological examination within normal limits. The diagnostic impression was a psychiatric disorders and alternately encephalopathy of unknown origin. Following a cranial computed axial tomography in which nothing is detected Psychiatry valuation is decided. The patient is admitted to Psychiatry and after several diagnostic tests are performed differential diagnosis; Dementia, depression or confused Mania Phase of Bipolar disorder, dissociative disorder, disorders resulting from alcohol consumption. During admission psychomotor restlessness recedes but continuous clouded, and gait disturbances are increasing appear. After
N. Lackner1 ° , A. Birner1 , S.A. Bengesser1 , F.T. Fellendorf1 , M. Platzer1 , R. Queissner1 , H.P. Kapfhammer1 , B. Reininghaus2 , E. Weiss3 , S.J. Wallner-Liebmann4 , E.Z. Reininghaus1 1 Medical University of Graz, Psychiatry, Graz, Austria; 2 Therapiezentrum Justuspark, Bva, Bad Hall, Austria; 3 Karl-Franzens University Graz, Biological Psychology, Graz, Austria; 4 Medical University of Graz, Pathophysiology and Immunology, Graz, Austria Introduction: Bipolar affective disorder has consequently related to overweight and obesity [1,2] as well as metabolic abnormalities [3]. Previous research also has suggested that cognitive deficits are associated with overweight and obesity in bipolar disorder [4]. In addition, impairments in social cognition so called Theory of Mind deficits are well established in bipolar disorder. Affect recognition abilites are related negative to clinical course of psychiatric patients [5]. Consequently, overweight and obesity have been associated with a worse course and psychiatric symptoms in bipolar disorder [2]. In the present study, we wanted to test the hypothesis that impaired Theory of Mind functions are associated with measures of overweight and obesity in a well characterized sample of euthymic individuals with bipolar disorder. Method: A group of 116 patients with bipolar affective disorder treated at the psychiatric outpatient-centre for bipolar affective disorder of the Medical University Graz was investigated with a social cognition task to measure facial affect recognition (the Reading the Mind in the Eyes (RMET)), and an anthropometric measurement set (Body mass index, Waist-to-Hip-Ratio, Weightto-Height-Ratio). Patients were diagnosed according to DSM-IV, and 38 patients additionally met criteria for the harmful metabolic syndrome (defined as a cluster of clinical and biochemical risk factors for cardiovascular disease and type 2 diabetes mellitus). In addition, a healthy control group (n = 83) was investigated using the same methods. Group differences were assessed with analyses of variance. To test associations between RMET performance and anthropometric measures, Pearson correlation coefficients were used. Results: Overall, our findings demonstrate an impaired performance on the RMET in patients with bipolar disorder compared with controls (F = 7.88, p < 0.01). The results suggest a negative
P.2.d. Mood disorders and treatment − Bipolar disorders (clinical) correlation between performance on the RMET and Waist-to-HipRatio in the bipolar Group(r = 0.23, p < 0.05). In addition, bipolar patients with metabolic syndrome had a worse performance in RMET than patients without metabolic Syndrome F = 3.22, p < 0.05). Conclusions: To the best of our knowledge, this is the first study that measured the relationship of overweight/obesity with social cognition function in bipolar disorder. In accordance with well-known cognitive deficits in bipolar disorder, also social cognition is impaired in this patient group, even in euthymia. Consequently, there is also a relationship between overweight/obesity and facial affects recognition in bipolar disorder. The current study has also some limitations: First, there was a higher prevalence of overweight and obesity in the patient sample. Second, the patients were on psychotropic medication and the effect of these treatments were unclear. Third, the cross-sectional design of this study does not allow for direct causal conclusions regarding the association beetwen overweight/obesity and social cognition deficits in bipolar disorder. More research is needed to investigate whether social cognition treatments reduce the risk for the development and maintenance of obesity in bipolar affective disorder. References [1] McElroy, S.L., Keck Jr, P.E., 2012. Obesity in bipolar disorder: an overview. Current Psychiatry Reports, 14(6), 650–658. [2] Lackner, N., Mangge, H., Reininghaus, E.Z., McIntyre, R.S., Bengesser, S.A., Birner, A., . . . Wallner-Liebmann, S.J., 2015. Body fat distribution and associations with metabolic and clinical characteristics in bipolar individuals. European archives of psychiatry and clinical neuroscience, 265(4), 313–319. [3] Vancampfort, D., Vansteelandt, K., Correll, C.U., Mitchell, A.J., De Herdt, A., Sienaert, P., . . . De Hert, M., 2013. Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators. American Journal of Psychiatry. [4] Lackner, N., Bengesser, S.A., Birner, A., Painold, A., Fellendorf, F.T., Platzer, M., . . . Fuchs, D. 2015. Abdominal obesity is associated with impaired cognitive function in euthymic bipolar individuals. The World Journal of Biological Psychiatry, 1−12. [5] Chen, Y., Cataldo, A., Norton, D.J., Ongur, D. 2012. Distinct facial processing in schizophrenia and schizoaffective disorders. Schizophrenia Research, 134(1), 95–100.
S439
is highly tolerated and shows lower rates of the side effects typically observed with other antipsychotic drugs, including sedation, weight gain, hyperprolactinemia, and extrapyramidal syndrome. Aim: To explore the efficacy, tolerability and safety of the combined approach with aripiprazole and natrium valproate in bipolar mania. Method: Eight patients participated in this observation. Inclusion criteria were a diagnosis of BAD with manic features, with or without psychotic features according to ICD-10. Patients were treated with the combination of natrium valproate and aripiprazole. At the 8 week follow-up patients were being treated with mean doses of aripiprazole (range 15−30 mg/day) and natrium valproate (range 1200–1800 mg/day). Every patient in this group had previously been unsuccessfully treated with one typical or atypical antipsychotic drugs as combination therapy with mood stabilizers. Clinical status was evaluated at baseline and at the 4 week and 8 week, follow-up using the total Young Mania Rating Scale (YMRS), Clinical Global Impressions Bipolar (CGI-BP) mania scale. Follow-up evaluations, using the same rating scale as at baseline, were undertaken 4 week and 8 week, from the start date of aripiprazole. Results: All patients (5 women and 3 men) aged between 23 and 45 years, completed 8 week of combination treatment. The results obtained indicate that aripiprazole added to natrium valproate treatment showed a beneficial effect on the general psychopathological symptomatology in a sample of BAD patients. The YMRS total score decreased significantly from baseline to 4 week and 8 week follow-up (p < 0.05). Significant improvements were also noted on the CGI-BP scores. Conclusion: Aripiprazole and natrium valproate combination is an effective and well-tolerated option in acute mania of BAD with therapeutic benefit for patients who are partially responsive to other drugs combinations. Natrium valproate /aripiprazole combination provides greater improvement in mania, and it appears to be safe with a lower risk of metabolic syndrome, without increased risk of adverse effects, compared with other medications combination. References
P.2.d.034 The combined approach with aripiprazole and natrium valproate in bipolar mania S. Bise1 ° , G. Sulejmanpaˇsi´c2 1 Psychiatric hospital Sarajevo, women, Sarajevo, Bosnia and Herzegovina; 2 University of Sarajevo Clinical Center- Psychiatric clinic, clinical, Sarajevo, Bosnia and Herzegovina Background: Bipolar afective disorder (BAD) is a chronic illness that is characterized by recurrent episodes of mania, depression or mixed symptoms. BAD has a prevalence of approximately 2−4% in the general population and is associated with a substantial rates of recurrence, interepisodic dysfunction, comorbidity, and premature mortality. Mania is one of the most difficult to treat manifestations of BAD and antipsychotic drugs play a major therapeutic role in this respect. Patients with BAD require combined therapeutic approach because of the cyclic disorder nature. Many studies report the combination of mood-stabilizing agents with atypical antipsychotics. Aripiprazole is approved for the acute management and maintenance of manic and mixed episodes associated with BD. Aripiprazole acts as a serotonin 5-HT2A receptor antagonist, as well as a partial agonist of the serotonin 5-HT1A and dopamine D2 receptors. It can be safely used, as it
[1] Vieta, E., T’joen, C., Mcquade, R.D., Carson, W.H. Jr., Marcus, R.N., Sanchez, R., Owen, R., Nameche, L., 2008. Efficacy of adjunctive aripiprazole to either valproate or lithium in bipolar mania patients partially nonresponsive to valproate/lithium monotherapy: a placebocontrolled study. American Journal of Psychiatry 165, 1316–1325. [2] Scherk, H., Pajonk, F.G., Leucht, S., 2007. Second-generation antipsychotic agents in the treatment of acute mania: a systematic review and meta-analysis of randomized controlled trials. Arch Gen Psychiatry 64, 442–455. [3] Marcus, R., Khan, A., Rollin, L., Morris, B., Timko, K., Carson, W., Sanchez, R. 2011. Efficacy of aripiprazole adjunctive to lithium or valproate in the long-term treatment of patients with bipolar I disorder with an inadequate response to lithium or valproate monotherapy: a multicenter, double-blind, randomized study. Bipolar Disorders. 13, 133–144. [4] Keck, P.E. Jr, Marcus, R., Tourkodimitris, S., Ali, M., Liebeskind, A., et al., 2003. A placebo-controlled, double-blind study of the efficacy and safety of aripiprazole in patients with acute bipolar mania. Am J Psychiatry 160, 1651–1658.