The Role of Clozapine as a Mood Regulator in the Treatment of Rapid Cycling Bipolar Affective Disorder. / Klozapinin Hizli Döngülü Bipolar Afektif Bozuklukta Duygudurum Düzenleyicisi Olarak Rolü.

OBJECTIVE: In this study, we aimed to investigate the effect of the clozapine on the course of the rapid cycling Bipolar Affective Disorder. METHOD: The study group was formed with the patients aged between 18 and 65 years of age, who met the criteria for the diagnosis of Bipolar Affective Disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition, with rapid cycling characteristics. Variables like the number of mania and depressive episodes, the days spent in mania and in depression and the number of hospitalization and attempted suicide, in the year before starting clozapine were determined and compared with the annual data after starting the clozapine. RESULTS: Eleven female and two male patients who met the inclusion criteria were included in this study. The group`s average daily use of clozapine was 180 mg (25-600 mg). There was a statistically significant difference in the number of days spent in the depression, the days spent in the mania, the number of depressive episodes and manic episodes, the number of hospitalizations and the suicide attempts after the clozapine use. CONCLUSION: In this study, it was determined that clozapine was effective as a mood stabilizer in Bipolar Affective Disorder treatment. The results show that clozapine reduces the episode frequency and the duration in rapid cycling Bipolar Affective Disorder which does not respond to all conventional treatments, including lithium, valproic acid, carbamazepine and antipsychotic drugs.

[Reliability and Validity Study of the Turkish Version of Hypomania Checklist-32-Revised]. / Hipomani Soru Listesi-32-Yenilenmis Sürümün Türkçe Güvenilirlik ve Geçerlilik Çalismasi.

OBJECTIVE: In this study, it is aimed to evaluate the reliability and validity of the Turkish version of Hypomania Checklist-32-Revised. METHOD: The study was carried out with 80 patients diagnosed with bipolar I disorder, 26 patients diagnosed with bipolar II disorder and 42 patients diagnosed with major depressive disorder attending the out- and in-patient psychiatry departments of three university hospitals and one training hospital, and 116 healthy volunteers consisting of university students. Mean duration of illness was 15,1 years for the bipolar disorder group, and 9,3 years for the major depressive disorder group. For concurrent validity, Mood Disorder Questionnaire was used. In the statistical analysis, internal consistency coefficient, item-total score correlation coefficients, exploratory factor analysis, correlation with concurrent scale and ROC curve were calculated. RESULTS: Translation into Turkish and back-translation into English of Hypomania Checklist-32-Revised were performed and thus the semantic harmony of the scale was obtained. In the internal consistency, Cronbach alpha coefficient was 0,914 and item-total score correlations were between 0,235-0.743. Solely the coefficient of item #23 was found as 0,110. In factor analysis, six factors were obtained but a two-factor solution representing 44,5% of the total variance was accepted and first factor represents overactivity and being expansive, second factor represents impulsivity and risky behaviors. Correlation of Hypomania Checklist-32-R with Mood Disorder Questionnaire was r=0,379. In the ROC analysis, the cut off point of the scale was calculated as 14 with a sensitivity of 71,0 and specificity of 69,8. The scale discriminates well between the bipolar group, and depressive and control groups. CONCLUSION: Hypomania Checklist-32-Revised developed for screening hypomania is reported to be reliable and valid in Turkish after cutting out item #23.

The Turkish Adaptation, Validity, and Reliability of the Internal States Scale.

INTRODUCTION: The Internal State Scale (ISS) was developed to simultaneously assess manic and depressive symptoms in bipolar disorder. In the present study, the validity and reliability of the Turkish version of ISS (ISS-TR) were examined. The present study aimed to present the psychometric properties of this scale. METHODS: The sample consisted of 200 outpatients with bipolar disorder and 49 healthy controls. Participants completed the Turkish Internal State Scale (ISS-TR), the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale (HDRS), and the Young Mania Rating Scale (YMRS). RESULTS: Reliability analyses revealed that the Cronbach alfa coefficient of ISS was 0.88 for the whole sample. Item-total correlations ranged from 0.15 to 0.78. Two factors emerged as a result of factor analysis: "mania" and "depression-well-being." Test-retest correlations were determined for the mania subscale as r=0.654, p<0.01 and for the depression-well-being subscale as r=0.356, p<0.01. The correlations between BPRS and both subscales were quite high. The correlation between HDRS and the depression-well-being subscale was higher (r=0.475) than that between HDRS and the mania subscale, whereas the correlation between YMRS and the mania subscale was higher (r=0.818) than that between YMRS and the depression-well-being subscale. It was seen that ISS could discriminate between the clinical and healthy control samples. In addition, it was observed that the mania subscale predicted a manic period more strongly, while the depression-well-being subscale predicted a depressive period better. CONCLUSION: ISS is a valid and reliable scale that can be used to simultaneously assess manic and depressive symptoms. It is thought that ISS will be useful in the recognition of prodromal symptoms and in the process of maintenance treatment.

First-episode psychosis is associated with oxidative stress: Effects of short-term antipsychotic treatment.

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.

[The relationship between the duration of drug use and the bipolar disorder patients' sociodemographic and clinical characteristics]. / Bipolar bozukluk hastalarinin ilaç kullanim sürelerinin sosyodemografik ve hastalik özellikleri ile iliskisi.

OBJECTIVE: The purpose of this study was to determine the duration of psychotropic drug use in the long-term follow-up of bipolar disorder (BD) patients. In addition, this study aimed to investigate their role in the daily clinical practice in association with patient sociodemographic and clinical characteristics. The overarching goal for this study was to produce results that enlighten the development of new treatment strategies. METHOD: Follow-up data acquired from the Psychiatry Department of Uludag University Faculty of Medicine was used to retrospectively evaluate 151 patients diagnosed with BD. Socio-demographic data of the patients and information regarding the disease and the drugs used were analyzed. RESULTS: Of the patients studied, 57.0% were female with a mean age of 41.5±12.8. The mean duration of follow-up was 1985.3±1933 [median 1291 (15-9135)] days; euthymic period accounted for 86.0% of this duration. Interestingly, incompliance with the treatment triggered the switch to mania and ineffective treatment triggered the switch to depression. Medication distribution was as follows: 95.4% of the patients received antipsychotic and mood stabilizer treatments, 3.3% received only mood stabilizer treatment, and 1.30% received only antipsychotic treatment. The major findings of this study was that many sociodemographic as well as clinical manifestations including, early onset (aged ≤18 years), unmarried, first episode of mania, those with disease not showing seasonal features, psychotic symptoms, history of hospitalization, and higher number of manic or hypomanic episodes resulted in increased patient prescribed antipsychotic drugs CONCLUSION: Our data suggests that antipsychotic drugs are being used more frequently and for longer durations in the treatment of BD.

[The validity and reliability of the Brief-Hypomanic Attitudes and Positive Predictions Inventory-Turkish version]. / "Hipomanik Tutumlar ve Pozitif Yordamalar Ölçegi" kisa formunun geçerlik ve güvenilirlik çalismas.

OBJECTIVE: There has been a great deal of interest in specific dysfunctional beliefs that may be associated with susceptibility to mania. The Hypomanic Attitudes and Positive Predictions Inventory (HAPPI) was developed by Mansell (2006) to identify such beliefs. The present study aimed to measure the psychometric properties of the Turkish version of the brief version of the HAPPI (Brief-HAPPI-TR). METHOD: The study sample consisted of 115 outpatients with bipolar disorder (BD) and 103 healthy controls. Participants were administered the Brief-HAPPI-TR, Mood Disorder Questionnaire (MDQ), and Dysfunctional Attitudes Scale (DAS). RESULTS: The reverse-scored HAPPI items lowered the alpha coefficient and were therefore excluded from the total score. The remaining items had high internal consistency for the entire sample (r = 0.84), for the BD group (r = 0.83), and for the control group (r = 0.86). The test-retest reliability coefficient was moderately high (r = 0.41). Brief-HAPPI-TR scores were significantly correlated with MDQ and DAS scores. Finally, Brief-HAPPI-TR was able to differentiate between the BD patients and controls. CONCLUSION: Brief-HAPPI-TR was observed to be valid and reliable for assessing hypomanic attitudes in Turkish BD patients in remission. In addition, we think that within the cognitive-behavioral paradigm this scale can be used to identify and treat dysfunctional cognitions in Turkish BD patients.

Sociodemographics, clinical features, and psychiatric comorbidities of patients with psychogenic nonepileptic seizures: experience at a specialized epilepsy center in Turkey.

Patients with psychogenic nonepileptic seizures (PNESs) or pseudoseizures are known to have psychiatric comorbidities. In the present retrospective analysis, we examined the sociodemographics, clinical characteristics, and psychiatric diagnoses of patients with PNESs. Our aim is to demonstrate the contribution of the consulting psychiatrists to the presumed psychiatric diagnoses of the neurologists. We used data from long-term video EEG monitoring (LVEM) performed at a specialized epilepsy center in Turkey. The study group comprised 67 patients (mean age: 30 years, 75% female) diagnosed with PNESs following LVEM of approximately 5 days' duration. Two hundred thirty-three episodes were recorded. Most of the patients experienced a PNES on the first day. All of the patients were taking antiepileptic drugs (AEDs) at the time of admission; 56.7% were taking antidepressant (AD) drugs. All of the PNES patients were diagnosed with conversion disorder by both the neurologists and the psychiatrists. Most of the PNES patients were using multiple AEDs. Cooperation between neurologists and psychiatrists and ongoing education for both neurologists and psychiatrists about PNES are needed in appropriate diagnosing and management of patients with PNES.

Metabolic, endocrinologic and cardiac effects of amisulpride: a 24-week follow-up study.

BACKGROUND: Amisulpride is a second-generation antipsychotic which has been proved to be effective in the control of both positive and negative symptoms of schizophrenia. In this study we aimed to determine metabolic, endocrinologic and cardiac effects of amisulpride commonly used in our clinical practice. METHODS: A total of 18 patients (11 males, 7 females) diagnosed with schizophrenia received amisulpride at the dosage of 800 mg/day and were followed up for 24 weeks. Positive and negative psychotic symptoms, extrapyramidal and sexual side effects, metabolic, endocrinologic and cardiac parameters were evaluated at regular intervals. RESULTS: Significant improvement in both positive and negative symptoms was observed in patients starting from the second week of treatment. Prolactin levels increased significantly both in men and women starting from the measurement on day 4. Prolactin elevation was significantly higher in women than in men. Increase in total cholesterol level became significant at week 24. No other significant difference was observed between weeks 1 and 24 regarding the other parameters. CONCLUSIONS: The clinical data from the present study supports the fact that amisulpride is an effective and safe antipsychotic drug, but elevates prolactin levels in both sexes.

Reversible escitalopram-induced hypothyroidism.

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.

Are there differences between serotonergic, noradrenergic and dual acting antidepressants in the treatment of depressed women?

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.

Efficacy and tolerability of switching to ziprasidone from olanzapine, risperidone or haloperidol: an international, multicenter study.

To compare the effectiveness of a switch from haloperidol (N=99), olanzapine (N=82), or risperidone (N=104) to 12 weeks of treatment with 80-160 mg/day ziprasidone in patients with stable schizophrenia or schizoaffective disorder. Stable outpatients with persistent symptoms or troublesome side effects were switched using one of three 1-week taper/switch strategies as determined by the investigator. Efficacy was assessed using the Brief Psychiatric Rating Scale score, Clinical Global Impression, Positive and Negative Symptom Scale, Montgomery-Asberg Depression Rating Scale, and the Global Assessment of Functioning Scale, and tolerability by using standard measures of weight change, extrapyramidal symptoms, and laboratory findings. Suboptimal efficacy was the primary reason for switching. The preferred switch strategy was immediate discontinuation, and the preferred dosing regimen was 120 mg/day. Completer rates were 68, 60, and 86% in the haloperidol, risperidone, and olanzapine pre-switch groups, respectively. At week 12, a switch to ziprasidone resulted in statistically significant improvement from baseline on the Brief Psychiatric Rating Scale score, Clinical Global Impression-Improvement, Positive and Negative Symptom Scale, and Global Assessment of Functioning scales, reduction in extrapyramidal symptoms and a neutral impact on metabolic parameters. Switch from olanzapine and risperidone resulted in weight reduction and from haloperidol in some weight increase. In conclusion, oral ziprasidone of 80-160 mg/day with food was a clinically valuable treatment option for stable patients with schizophrenia or schizoaffective disorder experiencing suboptimal efficacy or poor tolerability with haloperidol, olanzapine, or risperidone.

Delayed diagnosis of a neuroBehçet patient with only brainstem and cerebellar atrophy: literature review.

We report a 34-year-old male neuroBehçet's Disease (NBD) patient with atypical magnetic resonance imaging (MRI) findings, whose behavioral problems were followed by progressive neurological symptoms. The patient was hospitalized due to forgetfulness, irritability, behavioral dyscontrol and a choking sensation. T2-weighted MRI showed prominent atrophy of cerebellar hemispheres, the cerebellar peduncle, the midbrain and the pons. He was diagnosed with NBD after an evaluation of his medical history together with neuropsychiatric and laboratory findings. There are few reports of NBD with only brainstem and cerebellar atrophy. We discuss our patient in the context of the four previously reported cases. In NBD without evident mucocutaneo-ocular symptoms, neurologists should always consider the medical and family history. Early diagnosis of NBD helps to initiate appropriate treatment, thereby modulating the course of the disease and preventing complications.

[Reliability and validity of the Turkish version of the Social Adaptation Self-Evaluation Scale (SASS)]. / Sosyal Uyum Kendini Degerlendirme Olçegi (SUKDO) Türkçe formunum geçerlik ve güvenilirligi.

OBJECTIVE: SASS is a new self-evaluation scale that assesses the level of social functioning in depressed patients for clinical research purposes. The aim of this study was to investigate the validity and reliability of the Turkish version of SASS. METHOD: Data were obtained from 2 different sample groups that had no physical disturbances that could impair social functioning; healthy participants between the ages of 18 and 65 years (n = 66) and patients (n = 227) diagnosed with major depressive disorder (MDD). Assessment tools used in the study were SASS, Hamilton Depression Rating Scale, 17-item version, and Global Assessment of Functioning Scale. RESULTS: In the reliability analysis of both groups combined and the MDD group Cronbach's alpha values for the internal consistency of the scale were 0.90 and 0.87, respectively. Item-total score correlations were between 0.22 and 0.66 for both groups combined, and between 0.21 and 0.59 for the MDD group. The correlation coefficient of the scale's test-retest reliability was 0.770 (P < 0.0001) and the SASS value rose from 29.4 +/- 8.1 to 37.8 +/- 8.1 following treatment of depression (P < 0.0001). Four factors with Eigen values > 1 were obtained from the factor analysis. Factor 1, with an Eigen value of 7.169 explained 35.8% of the total variance and represented the entire scale alone. CONCLUSIONS: The Turkish version of SASS, as the original scale, demonstrated adequate validity and reliability for the measurement of loss of social functioning in MDD patients and demonstrated that scores changed in accordance with treatment for depression.

Predictive factors for time to remission and recurrence in patients treated for acute mania: health outcomes of manic episodes (HOME) study.

OBJECTIVE: To determine the time to remission and recurrence in patients treated for acute mania and the predictive factors associated with these outcomes. METHOD: This observational study, conducted in Turkey from April 2003 to January 2005, included patients with a DSM-IV diagnosis of bipolar I disorder, acute manic or mixed episode who were eligible to have an oral medication initiated or changed for the treatment of the episode. The patients were followed-up for 12 months. RESULTS: A total of 584 patients (mean ± SD age = 33.9 ± 11.2, 55.2% outpatients) were enrolled in 53 centers. Eighty-five percent of patients had a manic episode at baseline, with a mean ± SD duration of 21.6 ± 24.4 days. The baseline mean ± SD Clinical Global Impressions scale for use in bipolar disorder and Young Mania Rating Scale (YMRS) scores were 4.9 ± 0.9 (median = 5.0) and 33.2 ± 9.3 (median = 33), respectively. 539 patients achieved remission and, of those, 141 patients had recurrence. One-year remission and recurrence rates were 99.0% and 35.7%, respectively. Mean ± SD times to remission and recurrence in descriptive statistics were 80.9 ± 73.8 (median = 50) and 159.0 ± 95.5 (median = 156) days, respectively. In Cox regression analysis, psychiatric comorbidities (p = .048), a higher YMRS score (p < .001), and a higher number of previous depressive episodes (p = .009) were statistically significant predictors of a longer time to reach remission. Index episodes of longer duration (p = .033) and mixed type (p = 0.49) were significant predictors of a shorter time to recurrence. Confounding factors like concomitant treatment, comorbidities, and lack of blinding and randomization were other limitations. CONCLUSION: Predictors for a longer time to remission were psychiatric comorbidities, a higher YMRS score, and a higher number of previous depressive episodes. Predictors for a shorter time to recurrence were episodes of longer duration and mixed type.

Effects of various antidepressants on serum thyroid hormone levels in patients with major depressive disorder.

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.