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Aims In the present study, our aim was to investigate the oxidative-antioxidative systems in unmedicated first-episode psychosis (FEP) patients at the beginning and after short-term treatment. Methods This study consisted of 29 patients who experienced an FEP and 25 control subjects. In order to investigate the oxidative status, we determined plasma malondialdehyde (MDA) levels, oxidizability of red blood cells, oxidation and oxidizability of apolipoprotein B-containing lipoproteins (apo B-basal MDA and apo B-ΔMDA). In order to evaluate the antioxidative defense, we measured serum total antioxidative capacity, uric acid, albumin, total bilirubin and vitamin E levels and serum paraoxonase/arylesterase, whole blood glutathione peroxidase (GPx) and red blood cell superoxide dismutase activities before and after 6 weeks of treatment in patients with FEP. Results Plasma MDA and apo B-basal MDA levels and red blood cell superoxide dismutase activity were significantly higher and serum arylesterase and whole blood-GPx activities were lower in the FEP group than those of the healthy control group. There were not any significant changes in the oxidative and antioxidative system parameters (except increased vitamin E levels) after treatment. Conclusions The results of this study suggest that FEP is accompanied by oxidative stress. However, further studies are needed to clarify the role of oxidative stress in the physiopathologic mechanisms of FEP, so that oxidative and antioxidative system parameters can be used in the management of these patients. In accordance with psychiatric evaluation, for a better management, patients with FEP may require a multidisciplinary approach, including oxidative and antioxidative system parameters.

INTRODUCTION Comorbid depression in schizophrenia is associated with poor outcome, increased risk of relapse and a high rate of suicide. Identification of depressive symptoms and their appropriate treatment is crucial for depressed schizophrenic patients. The aim of this study is to investigate the rates of antidepressant prescription and their outcomes. METHODS The records of the schizophrenic outpatients, who were consulted at Psychosis Unit of Psychiatry Department between January 2007 and September 2012, were evaluated retrospectively. Enrolled schizophrenic patients' antidepressant medications were at their minimal effective doses and effective duration. RESULTS The present study demonstrates that 39 of the 101 patients during their follow-ups were prescribed antidepressants. The mean follow-up period was 6.3 (±4.2) years; the mean age at onset was 22 (±6.5) years; the mean duration of illness was 14.7 (±7.3) years and the mean number of psychotic exacerbation was 5 (±3.7). The most prescribed antidepressants were; sertraline (36.9%), venlefaxine (23.8%) and essitalopram (20.2%). SSRI's were prescribed 57 (73.1%), where as SNRI's 21 times (26.9%). There was no significant difference between SSRI (78.6%) and SNRI (21.4%) treatments in terms of psychotic exacerbation under antidepressant medication. Full remission of depressive symptoms was achieved in 21 patients (53.8%). Remission rates were significantly higher (p

ObjectiveThe aim of the current study is to determine whether serum levels of brain-derived neurotrophic factor (BDNF) and interleukin-2 (IL-2) can be biological indicators for the diagnosis of schizophrenia in patients with depressive symptoms.MethodForty-seven patients (11 patients diagnosed with schizophrenia, 16 patients diagnosed with schizophrenia and comorbid depression and 20 patients diagnosed with major depressive disorder) and 20 healthy subjects were enrolled. The Positive and Negative Symptoms Scale, the Calgary Depression Scale for Schizophrenia and the Hamilton Depression Rating Scale were used for assessment. The serum BDNF and IL-2 levels of all the subjects were studied.ResultsDecreased levels of serum BDNF and increased levels of serum IL-2 were found in the patients diagnosed with either schizophrenia, schizophrenia with depression, or major depressive disorder (p = 0.049, p = 0.010; p = 0.001 and p = 0.044; p = 0.027, p = 0.003; respectively) compared with control group. There were no significant differences between the patient groups in their serum BDNF and IL-2 levels.ConclusionsThe present study suggests that neurotrophic factors and immune system changes are involved in the pathogenesis of schizophrenia with or without depressive symptomatology. However, the data do not clarify whether depressive symptoms in schizophrenia occur as a dimension of schizophrenia or as symptoms of major depression that is comorbid with schizophrenia.

Objective: This paper aims to compare the efficacy and safety of three widely used antidepressants, sertraline, reboxetine, a sertraline-reboxetine combination and venlafaxine, in the treatment of MDD and their effect on depressive symptoms in MDD patients. Methods: A total of 206 patients were included in reboxetine, venlafaxine, sertraline, and sertraline-reboxetine combination groups; however 37 cases dropped out during the study period. The remaining 169 patients were distributed to groups as follows: reboxetine: 43, venlafaxine: 43, sertraline 42, sertraline-reboxetine combination group: 41. The data from patients, who were included and completed the previous four open-label studies, were pooled in the current study. Results:Treatment groups did not differ in terms of depression-related and sociodemographic features. There were no significant differences among treatment groups in terms of efficacy, safety, and remission. The reductions in HDRS scores as percentages were higher in venlafaxine group compared to sertraline group at visit 2 and visit 3 [p=0.001, ES: 0.1404 (large) and p=0.002, ES: 0.1109 (medium), respectively] and to the sertraline-reboxetine combination group at visit 2 and visit 3 [p=0.006, ES: 0.0910 (medium) and p=0.004, ES: 0.1023 (medium), respectively]. In addition, percentage changes of HDRS scores were higher in the reboxetine group compared to sertraline group at visit 2 [p=0.023, ES: 0.0615 (medium)]. HDRS items 1, 7, 10, 11, 13, and 14 formed the total HDRS score of all patients in remission. Conclusions: The antidepressants acting through different neurotransmitter systems display similar efficacy, though they are effective on different depressive symptoms or symptom clusters. Those treatment strategies also differed from each other in terms of onset of antidepressant efficacy. Despite its limitations, due to the lack of studies on this issue in the literature, the present stuydy is a valuable preliminary study. Bu araştırma major depresif bozukluk (MDB) tedavisinde sıkça kullanılan sertralin, reboksetin, venlafaksin ve sertralin-reboksetin kombinasyonunun depresif belirtiler üzerine etkisi ile bu tedavilerin etkililik ve güvenlik açısından birbiriyle karşılaştırılmasını amaçlamıştır. Yöntem: Daha önceki dört çalışmaya alınmış ve bu çalışmaları tamamlamış hastaların verileri bir arada değerlendirilmiştir. 206 hasta reboksetin, venlafaksin, sertralin ve sertralin-reboksetin kombinasyon gruplarına dahil edilmiş olup 37 hasta çalışmaları tamamlayamamıştır. Kalan 169 hastanın 43’er tanesi reboksetin ve venlafaksin, 42’si sertralin, 41’i sertralin- reboksetin kombinasyon grubunda yer almaktaydı. Bulgular: MDB klinik özellikleri ile sosyodemografik özellikler açısından gruplar arasında fark yoktu. Hamilton Depresyon Derecelendirme Ölçeği (HAM-D) değerlerindeki yüzdelik düşüş venlafaksin grubunda vizit 2 ve 3’te sertraline göre [sırasıyla p=0.001, ES: 0.1404 (büyük) ve p=0.002, ES: 0.1109 (orta)] ve sertralin-reboksetin kombinasyonuna göre vizit 2 ve 3’te [sırasıyla p=0.006, ES: 0.0910 (orta) ve p=0.004, ES: 0.1023 (orta)] daha yüksek olduğu saptanmıştır. Yine HAM-D değerlerindeki yüzdelik düşüş reboksetin grubunda sertraline göre vizit 2’de daha yüksek bulundu [p=0.02, ES: 0.0615 (orta)]. En sık rastlanan kalıntı belirtileri 1., 7., 10., 11., 13., ve 14. HAM-D maddeleriydi. Sonuç: Farklı nörotransmiter mekanizmaları üzerinden etki etmekle beraber bu çalışmadaki antidepresanlar benzer etkililik göstermişlerdir. Bununla beraber her tedavi yöntemi farklı belirti ve belirti grupları üzerinde etkili bulunmuş, antidepresan etkililiğin ortaya çıkış zamanları açısından farklılık göstermişlerdir. Bir takım kısıtlılıklarına karşın, bu alandaki çalışmaların az olması da göz önüne alındığında, bu çalışmanın bir ön çalışma olarak literatüre katkı sağlayacağı kanısındayız.

A total of 62 patients with major depressive disorder were analyzed in the study. Patients were evaluated for 11 weeks in an open label design to investigate the differential effects of reboxetine, sertraline and venlafaxine on thyroid hormones. Serum thyrotrophin (TSH), thyroxine (T4) and free (f)T4 levels were measured before and after treatment. All groups showed significant improvement in HAM-D scores. TSH level significantly reduced and T4 level significantly increased in the reboxetine group, however TSH level significantly increased and T4 level significantly reduced in the sertraline group. Percent changes of TSH (p=0.007) and T4 (p=0.001) were significantly different between the reboxetine and sertraline groups. In the sertraline group, baseline TSH levels were correlated with response to treatment as determined by the change in HAM-D scores (p=0.03, r=0.648). There was a significant association between the percent changes in TSH values and the reduction in HAM-D scores in the reboxetine group (p=0.03, r=-0.434). In the whole study group, female patients had lower values of basal T4 compared with men (P=0.043), however percent changes of T4 did not differ between genders. In the treatment-responders significant increase in the reboxetine group and significant decrease in the sertraline group regarding the T4 values were found. We observed that various antidepressants had different effects on thyroid hormone levels and this could be attributed to the different mechanisms of actions of these antidepressants.

Major depressive disorder (MDD) is blaimed to play a role in the onset of coronary artery disease (CAD). The aim of the present study was to investigate serum paraoxonase/arylesterase activities and oxidation of apolipoprotein B-containing lipoproteins in patients with MDD. Oxidation of lipoproteins plays an important role in atherogenesis and the enzyme paraoxonase, has been shown to prevent lipoprotein oxidation. Furthermore, low paraoxonase activity was suggested to predict CAD. Eighty-six patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for MDD and 36 healthy control subjects were included in the study. Serum paraoxonase and arylesterase activities were determined spectrophotometrically. Malondialdehyde (MDA) levels of apolipoprotein B-containing lipoproteins were determined before (basal) and after incubation with copper-sulphate, that yielded basal- and Delta-MDA values, respectively. Serum paraoxonase/arylesterase activities were significantly reduced in the post-treatment group compared with the pre-treatment group. Basal-MDA (MDA) level was significantly higher in the MDD group compared with the control group. Delta-MDA level of the severe MDD group was significantly higher than that of the control group. There was a positive correlation between the oxidizability of apolipoprotein B-containing lipoproteins and the severity of the disease. Total cholesterol, HDL-cholesterol, LDL-cholesterol, apolipoprotein B levels were significantly higher and apolipoprotein AI levels were significantly lower in the MDD group compared with those of the control group. The findings of the present study suggest that: 1) antidepressant treatment might reduce serum paraoxonase activity/mass; 2) oxidation and oxidizability of apolipoprotein B-containing lipoproteins seem to be increased in MDD.

Objective The aim of this study was to compare the efficacy and tolerability of reboxetine in the treatment of major depressive disorder (MDD) and MDD with anxiety features to venlafaxine XR. Method Patients with MDD, aging 18 between 65 years, were randomly allocated to two groups receiving either open-label venlafaxine XR capsules (n = 50) or reboxetine tablets (n = 43). Subjects were administered Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Scale (HAM-A) at baseline and 2, 4, 7, 10 weeks after the baseline visit. Results Response rates to antidepressant treatment were significantly higher in the venlafaxine XR group at 10th week. When patients having anxious depression were analysed separately; response rate for anxiety of reboxetine group was significantly higher at 7th week only. Mean number of side effects were significantly higher in reboxetine group. Only one subject in each group was dropped out due to side effect. Conclusion We may suggest that reboxetine is as effective and tolerable as venlafaxine XR in the treatment of MDD and MDD with anxiety features, and it may be considered a treatment option to venlafaxine XR. Copyright © 2006 John Wiley & Sons, Ltd.

In the present study, our aim was to investigate the oxidative-antioxidative systems in unmedicated first-episode psychosis (FEP) patients at the beginning and after short-term treatment.This study consisted of 29 patients who experienced an FEP and 25 control subjects. In order to investigate the oxidative status, we determined plasma malondialdehyde (MDA) levels, oxidizability of red blood cells, oxidation and oxidizability of apolipoprotein B-containing lipoproteins (apo B-basal MDA and apo B-ΔMDA). In order to evaluate the antioxidative defense, we measured serum total antioxidative capacity, uric acid, albumin, total bilirubin and vitamin E levels and serum paraoxonase/arylesterase, whole blood glutathione peroxidase (GPx) and red blood cell superoxide dismutase activities before and after 6 weeks of treatment in patients with FEP.Plasma MDA and apo B-basal MDA levels and red blood cell superoxide dismutase activity were significantly higher and serum arylesterase and whole blood-GPx activities were lower in the FEP group than those of the healthy control group. There were not any significant changes in the oxidative and antioxidative system parameters (except increased vitamin E levels) after treatment.The results of this study suggest that FEP is accompanied by oxidative stress. However, further studies are needed to clarify the role of oxidative stress in the physiopathologic mechanisms of FEP, so that oxidative and antioxidative system parameters can be used in the management of these patients. In accordance with psychiatric evaluation, for a better management, patients with FEP may require a multidisciplinary approach, including oxidative and antioxidative system parameters.

WOS: 000356969000009 Objective: It is aimed to evaluate the prophylactic effect of flupenthixol decanoate in remitted BD patients. Methods: Remitted patients with bipolar disorder (BD), who had at least one mood episode each year in the last five years in spite of adequate pharmacotherapy, were included. Flupenthixol decanoate 20 mg/ml was administered in every two weeks. Hamilton Depression Rating Scale (HDRS), Young Mania Rating Scale (YMRS), Bipolar Disorder Functioning Questionnaire (BDFQ), General Assessment of Functionality (GAF) and Side Effect Rating Scale (UKU) were applied. Patients were followed up for 12 months. Results: Eight patients with a mean age of 34.7 +/- 7.5 were enrolled to the study. None of the patients were under monotherapy before the study enrollment. Three (37.5%) of the three patients were dropped out. The data of remaining 5 patients' were evaluated. At the end of the study mean number of mood episodes declined to 0.2 +/- 0.4 per year indicating a statistical significance and the mean score of BDFQ declined to 119.6 +/- 2.7. Conclusions: Flupenthixol decanoate significantly improved functionality and decreased the number of mood episodes allowing an alternative treatment even in remitted BD patients.

This is a case report of reboxetine induced erectile dysfunction, seminal emission and ejaculation during defecation and micturition. A 44 year old male who had been suffering from depression without any sexual dysfunction was put on venlafaxine XR treatment. Due to delayed ejaculation and occasional episodes of absence of ejaculation he was switched to reboxetine. At the second week of treatment he reported erectile dysfunction and premature ejaculation, and seminal emission and ejaculation during defecation and micturition occurred later at 8th week of treatment. After he was switched to sertraline 50 mg/day, his erectile dysfunction, premature and spontaneous ejaculation symptoms subsided in 2 weeks. Although reboxetine is reported to be free of sexual side effects, individual vulnerabilities to such unwanted effects should be considered, and sexual dysfunction should be assessed thoroughly during the treatment.

Objective: This is study aimed to determine if serum levels of brain derived neurotrophic factor (BDNF) can be used as a biological marker to make a distinction between the depressive episodes of bipolar disorder (BD) and recurrent major depressive disorder (UD). Methods: Patients between 18-65 years of age and diagnosed with BD and UD according to DSM-IV-TR diagnostic criteria, who were admitted to the outpatient clinic of psychiatry department were enrolled to the patient arm of the study. Volunteers between 18-65 years of age, who had no physical morbidity and clinical psychopathology according to DSM-IV-TR diagnostic criteria, were enrolled to the control arm of the study. There were 24 patients (11 BD and 13 UD) and 18 healthy volunteers. Patients were required to be drug naive for the past four weeks prior to the study enrollment. Hamilton Depression Rating Scale (HDRS) were applied to all patients. The serum levels of BDNF of all the subjects were studied. Results: There were no differences between groups in terms of sociodemographic variables. Total number depressive episodes were higher in BD group compared to UD group. There were no differences between BD and UD groups in terms of serum levels of BDNF. However, in patient group serum BDNF values were lower than the control group. Serum BDNF levels did not correlate with age, body mass index or gender in each group. Serum BDNF levels did not correlate with mean scores of HDRS or number of depressive episodes. Discussion: Considering the outcomes of the present study, serum BDNF levels did not demonstrate any significant difference between patient groups. However, serum BDNF levels were lower in patient groups compared to controls. For the time being there is no valid biological diagnostic marker for psychiatric disorders. The data of the present study is far from generating a biological marker for the distinction of depressive episodes of UD and BD.

Agmatine is an endogenous substance, synthesized from L-arginine, and it is proposed to be a new neurotransmitter. Preclinical studies indicated that agmatine may have an important role in the pathophysiology of schizophrenia. This study was organized to investigate plasma agmatine in patients with schizophrenia and in healthy controls. Eighteen patients with schizophrenia and 19 healthy individuals constituted the subjects. Agmatine levels in the plasma were measured using the HPLC method. The S100B protein level, which is a peripheral biomarker for brain damage, was also measured using the ELISA method. While plasma levels of agmatine in patients with schizophrenia were significantly increased (p < 0.0001) compared to those of healthy individuals (control), there were no significant changes in the levels of S100B protein (p = 0.660). An ROC (receiver operating characteristic) curve analysis revealed that measuring plasma agmatine levels as a clinical diagnostic test would significantly differentiate between patients with schizophrenia and those in the control group (predictive value: 0.969; p < 0.0001). The predictive value of S100B measurements was not statistically significant (p > 0.05). A multiple regression analysis revealed that the age of the patient and the severity of the illness, as indicated by the PANSS score, significantly contributed the plasma agmatine levels in patients with schizophrenia. These results support the hypothesis that an excess agmatine release is important in the development of schizophrenia. The findings also imply that the plasma agmatine level may be a potential biomarker of schizophrenia. (C) 2013 Elsevier Ltd. All rights reserved.

Ziprasidone and tardive dystonia: a case report and literature review A 40-year-old woman with the diagnosis of schizoaffective disorder had been treated with different typical and atypical antipsychotic drugs since the age of 26. Three months after self-discontinuing her medication, she experienced an exacerbation of her psychotic symptoms, so ziprasidone and valproic acid treatment were started. Six months after initiation of the treatment, tardive dystonia was developed involving the neck region. Discontinuation of ziprasidone produced no benefit; thus clozapine, 75 mg/day, was initiated both for psychotic symptoms and dystonia. Due to lack of improvement in the dystonia and because she suffered from side effects, the dosage of clozapine was decreased to 25 mg/day and botulinum toxin type A treatment was administered. She had partial improvement and repeated injections were planned. Although atypical antipsychotic drugs cause fewer extrapyramidal side effects than typical antipsychotics, we must be cautious when prescribing these drugs because of their disabling side effects.

Some drugs can cause alterations in the concentration of thyroid hormones in blood even without clinical signs of dysfunction or pathology of the thyroid gland. Apart from the well-known relationship between depression and hypothalamic-pituitary-thyroid (HPT) axis, and the impact of selective serotonin reuptake inhibitors (SSRIs) on thyroid indices, hypothyroidism is a very rare adverse effect of SSRI treatment. However, the case presented here demonstrates that escitalopram may have the potential to induce hypothyroidism without any significant clinical signs and symptoms. Therefore, the possibility of SSRI-induced asymptomatic hypothyroidism presented here may help clinicians in this regard.

Background. This study aims to investigate if there is a differential outcome of serotonergic and noradrenergic antidepressant treatment and if menopausal status has an impact on antidepressant response in depressed women. Methods. Data of the 111 depressed women who were included and completed the previous four open-label studies where patients were evaluated six times during a 10-week period, were pooled in the current study. Each of the reboxetine, sertraline and venlafaxine groups consisted of 37 depressed women. Patients were also divided into two subgroups of age, determining the 44 years as the cut-off point representing the menopausal status. Results. No significant difference was observed in the percent change of Hamilton Depression Rating Scale-17 (HDRS) and remission rates among treatment groups. Percent changes in Clinical Global Impression-Severity of Illness scale (CGI-S) and response rates were in favour of venlafaxine group at week 10. Individual HDRS items 2, 3, 4, 5 and 6 demonstrated significant improvement in the sertraline group, whereas HDRS item 7 demonstrated significant improvement in the venlafaxine group. An early reduction in anxiety subscale was observed in the venlafaxine group. Menopausal status had no impact on the outcome measures. Conclusions. These results suggest that noradrenergic and serotonergic activity do not differ from each other in treating depressed women. However, serotonergic activity appears to be more prominent in some particular symptoms such as feelings of guilt, suicidal ideation and sleep. Also, menopause does not appear to affect antidepressants' benefit in depressed women.

Objective The aim of the present study was to investigate the oxidative–antioxidative systems and effects of different antidepressants on these systems in patients with major depressive disorder (MDD). Method Ninety-six patients with a Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) diagnosis of MDD and 54 healthy controls were included in the study. Plasma malondialdehyde (MDA) levels and susceptibility of red blood cells (RBCs) to oxidation were determined to investigate the oxidative status, plasma vitamin E, vitamin C, serum total carotenoid levels, total antioxidant capacity (TAOC), RBC superoxide dismutase (SOD) and whole blood glutathione peroxidase (GPx) activities were measured to investigate the antioxidative defence before and after 6 weeks of antidepressant treatment. Results Plasma MDA levels and susceptibility of RBCs to oxidation were significantly higher in the MDD group compared with the control group. RBC SOD activity was significantly increased in patients with MDD, and furthermore there was a significant positive correlation between the severity of the disease and SOD activity. Conclusion MDD is accompanied with oxidative stress; however, oxidative–antioxidative systems do not seem to be affected by 6 weeks of antidepressant treatment. Copyright © 2007 John Wiley & Sons, Ltd.

Objective: Pain or painful physical complaints may be the sole complaint for admission to health care units in most of the major depression disorder (MDD) patients. In this study it is aimed to investigate the association between pain and depressive symptoms in depressed patients. Methods: A hundred patients, between 18-65 years of age and diagnosed with MDD according to DSM-IV-TR diagnostic criterion, who admitted to the outpatient clinic of Psychiatry department were enrolled to the study. Patients with accompanying axis I or axis II disorders according to DSM-IV-TR, patients with alcohol or substance abuse and patients whose pain complaints are attributable to an existing organic illness are excluded. Sociodemographic data form, Hamilton Depression Rating Scale (HDRS) which measures depression and Visual Analogue Scale (VAS) were applied to all patients who were enrolled to the study. Results: The mean age of the patients were 37.2±11.3 years, mean number of MDD episodes were 1.9±1.12, duration of the recent episode were 7.2±5.6 months and mean score of HDRS were 21.8±4.2. 47% of the patients had pain complaint. Duration of the painful complaints were 28.7±34.4 months, mean score of VAS was 55.8. The most painful complaint was headache. Mean number of painful complaint localization was 1.6±0.9. The painful complaints were found to be associated with more severe depression. Discussion: It is clear that there is an association between MDD and pain. It is also known that the course of depression is poorer in MDD patients with painful complaints. Thus, for clinical practice, painful complaints should be questioned in details and treatment options should arranged in this regard for better outcome in the treatment of MDD.