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Öğe Clinical potential of cariprazine in the treatment of acute mania(2013) Altmbas, Kürat; Guloksuz, Sinan; Oral, Esat TimuçinCariprazine (RGH-188, trans-4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]- ethyl}-N,N-dimethylcarbamoyl-cyclohexyl-Amine hydrochloride), is a novel antipsychotic with dopamine D2 and D3 receptors antagonist-partial agonist properties. Cariprazine has also moderate affinity for serotonin 5-hydroxytryptophan (5-HT) 1A receptors, high affinity for 5-HT1B receptors with pure antagonism and low affinity for 5-HT2A receptors. Randomized, double blind, placebo controlled, flexible-dose (3-12 mg/day) studies have demonstrated cariprazine is effective in both schizophrenia and acute manic episodes associated with bipolar disorder. The incidence of serious adverse events in cariprazine arm was no different than in placebo arm in these studies. The most common adverse events were extrapyramidal symptoms, headache, akathisia, constipation, nausea, and dyspepsia which can be explained with cariprazine's partial dopamine agonism. Although cariprazine treatment was associated with a higher incidence of treatmentemergent adverse events, particularly akathisia and tremor, common side effects of marketed second generation antipsychotics such as weight gain, metabolic disturbances, prolactin increase or QTc prolongation were not associated with cariprazine, probably due to its moderate to low binding affinity for histamine H1 and 5-HT2C receptors. Animal studies show that cariprazine may have additional therapeutic benefit on impaired cognitive functioning with D3 receptor activity, however clinical data is still scarce. The aim of this article is to review the potential use of cariprazine for the treatment of acute manic episodes in the light of the preclinical and clinical trials reported to date. © Medicinska naklada - Zagreb, Croatia.Öğe CLINICAL POTENTIAL OF CARIPRAZINE IN THE TREATMENT OF ACUTE MANIA(Medicinska Naklada, 2013) Altinbas, Kursat; Guloksuz, Sinan; Oral, Esat TimucinCariprazine (RGH-188, trans-4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexyl-aminehydrochloride), is a novel antipsychotic with dopamine D2 and D3 receptors antagonist-partial agonist properties. Cariprazine has also moderate affinity for serotonin 5-hydroxytryptophan (5-HT) 1A receptors, high affinity for 5-HT1B receptors with pure antagonism and low affinity for 5-HT2A receptors. Randomized, double blind, placebo controlled, flexible-dose (3-12 mg/day) studies have demonstrated cariprazine is effective in both schizophrenia and acute manic episodes associated with bipolar disorder. The incidence of serious adverse events in cariprazine arm was no different than in placebo arm in these studies. The most common adverse events were extrapyramidal symptoms, headache, akathisia, constipation, nausea, and dyspepsia which can be explained with cariprazine's partial dopamine agonism. Although cariprazine treatment was associated with a higher incidence of treatment-emergent adverse events, particularly akathisia and tremor, common side effects of marketed second generation antipsychotics such as weight gain, metabolic disturbances, prolactin increase or QTc prolongation were not associated with cariprazine, probably due to its moderate to low binding affinity for histamine H1 and 5-HT2C receptors. Animal studies show that cariprazine may have additional therapeutic benefit on impaired cognitive functioning with D3 receptor activity, however clinical data is still scarce. The aim of this article is to review the potential use of cariprazine for the treatment of acute manic episodes in the light of the preclinical and clinical trials reported to date.Öğe Electrocardiography changes in bipolar patients during long-term lithium monotherapy(Elsevier Science Inc, 2014) Altinbas, Kursat; Guloksuz, Sinan; Caglar, Ilker Murat; Caglar, Fatma Nihan Turhan; Kurt, Erhan; Oral, Esat TimucinObjective: Cardiovascular side effects of lithium have been reported to occur mainly at higher-than-therapeutic serum levels. We aimed to investigate the impact of the long-term lithium use on electrocardiogram (ECG) parameters in association with the serum levels in patients with bipolar disorder (BD) and in healthy controls (HCs) serving as the reference group. Methods: The study sample consisted of 53 euthymic BD type I patients on lithium monotherapy at therapeutic serum levels (M=0.76, S.D.=0.14, range=0.41-1.09 mmol/l) for at least 12 months and 45 HCs. A 12-lead surface ECG was obtained from all participants at resting state for at least half an hour for 5-min recording. Heart-rate, Pmax, Pmin, QRS interval, QT dispersion, QT dispersion ratio (QTdR) and Tpeak-to-end interval (TpTe) were measured. Results: Regression analyses revealed that QTdR (B=14.17, P=.001), TpTe (B=18.38, P<.001), Pmax (B=17.84, P<.001) and Pmin (B=25.10, P<.001) were increased in BD patients who were on chronic lithium treatment than in HCs after controlling for age, sex and strict Bonferroni correction for multiple testing. There were no associations between serum lithium levels and ECG parameters. Conclusion: Our findings suggest that the use of lithium is associated with both atrial and ventricular electrical instability, even when lithium levels are in the therapeutic range. (C) 2014 Elsevier Inc. All rights reserved.Öğe Evaluation of Antidepressant Choices for The Treatment of Depressive Symptoms in Patients with Bipolar Disorder(Yerkure Tanitim & Yayincilik Hizmetleri A S, 2012) Atagun, Murat Ilhan; Altinbas, Kursat; Yesilyurt, Sema; Yesilbas, Dilek; Guloksuz, Sinan; Oral, TimucinObjective: Antidepressants are thought to cause manic switches and accelerate cycling in the treatment of bipolar depression. On the other hand, other evidence suggests that antidepressant neither cause manic switches, nor are effective for the treatment of bipolar depression. This study aimed to assess clinicians' attitudes towards antidepressant choices for treatment of bipolar depressive episodes and subthreshold depression. Methods: Medical records of 784 patients with bipolar disorder were investigated retrospectively. Antidepressants were used in 55 of 263 depressive episodes (20.9%). Data regarding 78 episodes (23 subthreshold symptoms, 55 episodes) of 68 patients (54 female, 14 male; mean age: 39.64 +/- 10.99) were obtained. Descriptive statistics were the evaluation method. Results: In our department, antidepressants were used in 20.9% of the patients in the treatment of bipolar depression. One third of patients receiving antidepressant prescriptions had a history of manic switch, 5 (21.7%) of the patients with subthreshold symptoms receiving antidepressant prescriptions had a history of manic switch. However, manic switch occurred in only 5 (6.4%) patients. Selective serotonin reuptake inhibitors were the most common cause (58.3%) of the manic switch in patients with a history of manic switch. Discussion: Clinicians are still using antidepressants in the treatment of bipolar depression. Antidepressants targeting many neurotransmitter systems can be used in the first line treatments and antidepressants can be used even in patients with a history of manic switch. This controversial topic should be studied prospectively with larger samples and it must be clarified whether this phenomenon is a natural course of the disorder or triggered by antidepressant medications.Öğe Evaluation of the Association between Lithium Treatment and GSK-3? Polymorphism in Bipolar Disorder Patients(Turkiye Sinir Ve Ruh Sagligi Dernegi, 2018) Altinbas, Kursat; Yesilbas, Dilek; Ince, Bahri; Cansiz, Alparslan; Sılan, Fatma; Özdemir, Öztürk; Guloksuz, SinanObjective: There is a lack of evidence regarding clinical predictors for the treatment response to lithium, which is the main stay treatment option for bipolar disorder. Studies that examined the mechanistic action of lithium revealed that glycogen synthase kinase 3 beta (GSK-3 beta) enzymeinhibition was important in regard to treatment responses. Based on this background, we aimed to investigate the association between responses to lithium treatment and five different polymorphisms of GSK-3 beta. Method: Lithium treatment response scale (LTRS) scores for 100 patients diagnosed with bipolar disorders type I were calculated according to the hospital records. Blood samples were collected and genomic DNA was obtained using the MagNA Pure Compact automatic isolation method. The GSK-3 beta: rs17183904, rs17183897, rs34009575, rs34002644, and rs17183890 polymorphisms were analyzed by real time PCR. Results: In this cohort, the mean age of patients was 41.1 +/- 10.3 years, the mean age of disease onset was 24.5 +/- 8.2, and the mean LTRS score was 4.9 +/- 1.8. There was no statistically significant difference for LTRS scores between groups in terms of gender, marital status, level of education, and the type of first episode. LTRS was significantly higher in only the patients harbouring GSK-3 beta rs17183890 AG genotype (p=0.008, t: 2.71). Interestingly, no differences were found for the remaining polymorphisms. Conclusion: The specific GSK-3 beta polymorphism that associated with lithium-response in our study may help to predict lithium responses and to develop individualized treatment. We presume that our pharmacogenomic findings may also provide important contributions to the clinical practice in regard to future evaluation of the treatment adherence and side effects. To obtain these goals, further genome-wide scanning studies conducted on larger sample cohorts are required.Öğe Metabolic syndrome prevalence in different affective temperament profiles in bipolar-I disorder(Assoc Brasileira Psiquiatria, 2013) Altinbas, Kursat; Guloksuz, Sinan; Oral, E. TimucinObjective: Temperament originates in the brain structure, and individual differences are attributable to neural and physiological function differences. It has been suggested that temperament is associated with metabolic syndrome (MetS) markers, which may be partly mediated by lifestyle and socioeconomic status. Therefore, we aim to compare MetS prevalence between different affective temperamental profiles for each season in bipolar patients. Methods: Twenty-six bipolar type-I patients of a specialized outpatient mood disorder unit were evaluated for MetS according to new definition proposed by the International Diabetes Federation in the four seasons of a year. Temperament was assessed using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego - autoquestionnaire version (TEMPS-A). Results: The proportions of MetS were 19.2, 23.1, 34.6, and 38.5% in the summer, fall, spring, and winter, respectively. Only depressive temperament scores were higher (p = 0.002) during the winter in patients with MetS. Conclusion: These data suggest that depressive temperament profiles may predispose an individual to the development of MetS in the winter.Öğe Minor hemoglobins HbA2 and HbF associate with disease severity in bipolar disorder with a likely protective role of HbA2 against post-partum episodes(Elsevier, 2013) Ince, Bahri; Guloksuz, Sinan; Altinbas, Kursat; Oral, Esat Timuin; Alpkan, Latif Ruhsat; Altinoz, Meric A.Background: There exist studies indicating that bipolar disorder (BD) associates with changes in brain blood flow. Human brain with its high demand to oxygen constitutes 2% of the Loral body weight, while it receives 20% of cardiac output, a and 13;-,Ylobin chains of hemoglobin were recently found in neural tissues, yet no study has questioned blood hemoglobins in BD. Methods: A total of 120 euthymic BD patients (40 males and SO females) were analyzed via high performance liquid chromatography (1-IPLC) to measure minor hemoglobin levels, which were statistically compared with disease characteristics. Results: Minor hemoglobins HbA2 and HbF associated positively with episode density as a measure of disease severity in BD. An increased level of HbA2 meant significantly less postpartum episodes in child bearing women. HbF levels were higher in patients with a positive family history of any psychotic disorder. Sum of HbA2 and HbF correlated with episode density with a stronger significance (p <0001) supporting intermittent hypoxia hypothesis in 130. Limitations: The study was conducted only on euthymic patients to avoid likely bigger exogenous effects such as electro-convulsive therapy and diverse drug regimes, yet larger comparative studies are needed to support our current findings. Conclusions: Higher HbA2 and HbF in more severe bipolar disorder may be compensations against intermittent hypoxias in BD. HbA2 increases following myocardial angina and in mountain dwellers, which may indicate protective roles in extreme conditions. HbF increase may act more as a maladaptation or emerge via haplotypal associations of BD genes and gamma-globin locus at 11p15.5. (C) 2013 Elsevier B.V. All rights reserved,Öğe Temperament characteristics in patients with panic disorder and their first-degree relatives(W B Saunders Co-Elsevier Inc, 2015) Altinbas, Gulcin; Altinbas, Kurst; Guloksuz, Selin Aktan; Guloksuz, Sinan; Aydemir, Omer; Ozgen, GulizAim: Panic disorder is one of the highly heritable anxiety disorders; and temperament characteristics are considered predicting liability to panic disorder. Accumulating evidence suggests temperament characteristics are intermediate phenotypes for clinical conditions. Given this background, we aimed to investigate temperament characteristics in patients with panic disorder, their first-degree relatives, and healthy controls. Method: Study sample was consisted 60 patients with panic disorder, 37 first-degree relatives of these patients, and 37 age, gender, and education level matched healthy controls (HC). SCID-I, the Panic Agoraphobia Scale, and the State and Trait Anxiety Inventory were applied to assess clinical characteristics of the patient group. Temperament characteristics were assessed using the Temperament Evaluation of Memphis, Pisa, Paris, San Diego Autoquestionnaire (TEMPS-A). Results: Anxious, depressive, cyclothymic, and irritable temperament scores of patients were higher than those of HC. There was no difference between the patients and the relatives, with the exception of higher anxious temperament scores in patients. Conclusion: Overall, our findings suggest that anxious temperament characteristic might be a trait marker for liability to panic disorder. Further research with a prospective design in a larger sample is required to confirm our findings. (C) 2015 Elsevier Inc. All rights reserved.
