Tayfun Turan

A 12-month study of the efficacy of rivastigmine in patients with advanced moderate Alzheimer's disease

The efficacy of a centrally active cholinesterase inhibitor, rivastigmine tartrate (ENA 713), in patients with advanced moderate Alzheimer’s disease (AD) was evaluated in a 12-month placebo-controlled study. We aimed to investigate whether there was any evidence for the benefits of rivastigmine in patients with severe disease. These patients were compared with matched controls. In this study, 24 patients with advanced moderate AD received rivastigmine for 12 months. Another 20 patients received placebo. Mean daily doses of rivastigmine in the higher-dose group at 3, 6, 9, and 12 months were 6.1 ± 1.0, 8.3 ± 1.2, 8.9 ± 1.3, and 10.7 ± 1.6 mg/day, respectively. Cognitive abilities were assessed using the 11-item cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). Forty-five percent of placebo-treated patients declined by at least 4 points on the ADAS-cog. Conversely, only 18.3% of patients treated with rivastigmine declined by 4 or more points. Functional disabilities, as assessed using the Disability Assessment for Dementia Scale, remained significantly superior in rivastigmine-treated patients compared with placebo-treated patients. Patients benefited from high-dose rivastigmine treatment on all outcome measures, including the Mini-Mental State Examination, Progressive Deterioration Scale, as well as the Global Deterioration Scale. Patients receiving rivastigmine for 12 months significantly improved compared with placebo-treated patients (p < 0.001). By 52 weeks, patients originally treated with 6–12 mg/day rivastigmine had a significantly better cognitive function than patients originally treated with placebo. Long-term rivastigmine treatment appeared to be well tolerated in patients with advanced moderate AD and significantly benefits the cognitive and functional symptoms of AD.

The Effects of Electroconvulsive Therapy on GABAergic Function in Major Depressive Patients

Objectives: It has been proposed that major depression is associated with a dysfunction of the &ggr;-aminobutyric acid (GABA) system. This study was planned to investigate whether there are any alterations in GABAergic activities in major depressive patients and, if there are, whether electroconvulsive therapy (ECT) has any effect on these changes. Methods: Twenty-five depressed inpatients who responded to a course of ECT and 23 healthy subjects were included in the study. Serum GABA levels were measured 2 days before and 10 minutes after the first ECT and 3 days after the last ECT, and a baclofen challenge test was performed 2 days before the first ECT and 3 days after the last ECT in the patients. The same tests were carried out only once in the control group. Results: Depressive patients had lower serum GABA levels compared with healthy individuals, and ECT caused a significant increase in these levels. The acute effect of the one-ECT procedure was a huge increase in the baseline GABA levels. Although there was no difference in the maximum alteration in growth hormone with baclofen between the patients and controls before the therapeutic ECT course, it became significantly higher in the depressive patients than in the controls after the treatment. Conclusions: The findings of this study support the GABA deficit hypothesis of major depression because major depressive patients have lower levels of serum GABA that are increased by a completed ECT course. ECT seems to increase brain GABA levels as well as GABAB activity, and these effects may contribute to its mechanism of therapeutic effect.

Effects of short- and long-term lithium treatment on kidney functioning in patients with bipolar mood disorder

Lithium (Li) carbonate has been reported to be able to cause some reversible functional changes in the kidney. In this study, the authors aimed to investigate whether the duration of Li treatment is the primary determinant of the changes in renal functioning due to the Li treatment. For this purpose, 10 Li-naïve (mean age+/-S.D.: 34.50+/-4.85), 10 short-term (mean age+/-S.D.: 31.77+/-7.61) and 10 long-term (mean age+/-S.D.: 36.60+/-10.15) Li-treated bipolar patients were included in the study. Serum blood urea nitrogen (BUN) and creatinine, urine creatinine levels, creatinine clearance, urine osmolality before and after 8-h water deprivation and urine osmolality after desmopressin injection were measured in all patients. Serum BUN and creatinine levels were within the normal limits and not statistically different among the groups. Creatinine clearance of the long-term Li-treated group was significantly lower than both that of the Li-naïve group and that of the short-term Li-treated group. After 8-h water deprivation and also after desmopressin injection, no difference was found among the groups in terms of urine osmolality. However, when each patient was evaluated individually in terms of their renal concentrating ability, partial nephrogenic diabetes insipidus was diagnosed in four patients on long-term and in two patients on short-term Li treatment. To our surprise, hypothalamic diabetes insipidus was also diagnosed in other two patients on long-term Li treatment. These results demonstrate that long-term Li treatment may cause impairment in renal concentrating ability, some of which may originate from the effects of Li on vasopressin on hypothalamic level, and a decrease in glomerular filtration rate (GFR). In the light of these data, we can conclude that long-term administration of Li may be a risk factor for Li-induced renal impairment, which is a progressive effect in nature.

May oxytocin be a trait marker for bipolar disorder

There is evidence to suggest that oxytocin is effective in stabilizing mood in humans. Lower plasma oxytocin levels have been reported in patients with major depression. The objective of this study was to investigate serum oxytocin levels during manic and depressive episodes and in the remission period in patients with bipolar disorder. Twenty-two patients in manic episode, 21 in depressive episode, and 24 in remission at the initial phase, ranging from 18 to 65 years of age, who were diagnosed with BD Type I and 24 healthy individuals were included in this study. Blood samples were collected from subjects in the morning at the beginning of the study. A second blood sampling was obtained from manic and depressive patients after response to treatment. MANCOVA was performed to compare the oxytocin values of the groups. The serum oxytocin levels of patients in manic episode were statistically significantly higher than those of the depressive episode and remission groups and of the healthy subjects. The serum oxytocin levels of patients in the depressive episode group and in the remission group were statistically significantly higher than those of the control group. The serum oxytocin levels of the manic episode and depressive episode patients after response to treatment were statistically significantly higher than those of the control group, and there was no statistically significant difference between the patient groups in serum oxytocin levels. The higher oxytocin levels observed in patient groups, compared to the controls, before and after response to treatment suggest that oxytocin may be a trait marker in BD.

Effects of antidepressant treatment on thyrotropin-releasing hormone stimulation, growth hormone response to L-DOPA, and dexamethasone suppression tests in major depressive patients

Dexamethasone suppression (DST), thyroid-stimulating hormone (TSH) and prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) and growth hormone (GH) response to L-DOPA tests were evaluated in 19 depressed inpatients before the commencement of the antidepressant treatment and after the clinical response to examine: (i) the functional relationships among the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axis and dopaminergic system in depression, (ii) any alterations in these hormonal functions with the antidepressant treatment. TSH responses to TRH showed a tendency to increase from pre- to posttreatment period, while TRH-induced PRL and L-DOPA-induced GH responses did not change with treatment in depressed patients who responded to the treatment. Females showed significantly higher TSH and PRL responses to TRH compared to males. No interconnections were found among the responses in DST, TRH stimulation test and L-DOPA-induced GH test in the patients. The results do not support the interrelations between the abnormalities in the HPT and HPA axes and central dopaminergic activity in depression.

Relationship between depression and proinflammatory cytokine levels in hemodialysis patients.

Aim: To evaluate the presence of the relationship between depression and proinflammatory cytokine levels in hemodialysis (HD) patients. Methods: The study included 40 HD patients and 20 healthy controls. All participants were evaluated for the presence of depression using the structured clinical interview based on criteria defined by Diagnostic and Statistical Manual Mental Disorders (Fourth Edition, Text Revision) Axis I disorders. The severity of depressive symptoms was assessed using the Beck Depression Inventory, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale. The depressive patients received antidepressants for 8 weeks. Blood samples were taken at baseline and after 8 weeks of antidepressant treatment for interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) levels. Results: A total of 9 (22.5%) of the 40 HD patients had depression. IL-1, IL-6, and TNF-α levels were significantly higher in HD patients compared with that in the control group, but were not significantly different between HD patients with and without depression. In the depressive patients, we observed no significant difference in proinflammatory cytokine levels after antidepressant treatment. The psychometric measurements in depressive patients decreased significantly after antidepressant treatment. Conclusion: We observed that depression is a common psychiatric disorder and has no significant effect on proinflammatory cytokine levels in HD patients; no important improvement in cytokine levels was observed after antidepressant therapy.

Ultrasonically determined thyroid volume and thyroid functions in lithium-naïve and lithium-treated patients with bipolar disorder: a cross-sectional and longitudinal study

This study investigated thyroid volume, hormone levels and antibodies in long‐term lithium‐treated and lithium‐naïve bipolar patients, some of whom underwent prospective follow‐up evaluations.

Effects of electroconvulsive therapy on hypothalamic–pituitary–thyroid axis activity in depressed patients

In this study, the authors aimed to test the hypothesis that electroconvulsive therapy (ECT) may cause some alterations in hypothalamic-pituitary-thyroid (HPT) axis hormones and these responses may change throughout respective ECT sessions. Nineteen depressed inpatients (8 males, 11 females; mean age+/-S.D.: 44.77+/-10.59 years) considered suitable for ECT were included in the study. Each patient was exposed to 7 ECT sessions with general anaesthesia. The blood samples for measurements of thyroid-stimulating hormone (TSH), free thyroiodothyronine (fT3) and free thyroxine (fT4) were drawn before (baseline) and after propofol, immediately after ECT, and 30 and 60 min after ECT during the first and last (seventh) ECTs. In both the first and seventh ECTs, there was a significant increase in TSH levels 30 min after ECT compared to the pre-ECT values. Additionally, a significant decrease in post-ECT fT4 values compared to the baseline values was found only during the seventh ECT. No difference was detected in the TSH, fT3 and fT4 responses to ECT between males and females, and between bipolar and unipolar depressive patients. These results show that ECT may have some effects on the HPT system. However, whether there is a relationship between these neuroendocrine responses and the therapeutic effect of ECT is not clear.

Association between Depression, Nutritional Status, and Inflammatory Markers in Peritoneal Dialysis Patients

Background: To investigate the relationship between depression, nutritional status, and inflammatory markers in patients on peritoneal dialysis (PD). Patients and Methods: This prospective study included 40 PD patients and 20 healthy people. The severity of depressive symptoms was assessed using the Beck Depression Inventory, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale. The depressive patients received antidepressant drug for 8 weeks. Blood samples were taken before and after antidepressant treatment for the high-sensitive C-reactive protein (hs-CRP), interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α) levels. Results: Ten (25%) of the 40 PD patients had depression. No significant difference was determined between depressive patients and nondepressive patients. The mean erythrocyte sedimentation rate was higher in depressive patients. There was no significant difference for other inflammation parameters, including hs-CRP, TNF-α, IL-1, and IL-6, between depressive patients and nondepressive patients. In the depressive patients, we did not observe any significant change in nutritional parameters after antidepressant treatment. When we evaluated inflammation parameters of the depressive patients before and after antidepressant treatment, only IL-1 and IL-6 levels were significantly increased after antidepressant treatment. Conclusion: The depressive disorder in PD patients is a common psychopathology and has no significant effects on nutritional status and inflammation.

Hypothalamic-Pituitary-Adrenal Axis Response to Oral Naltrexone in Alcoholics during Early Withdrawal

INTRODUCTION It is thought that naltrexone may play a significant role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis response to stress. We investigated the HPA axis response following single-dose oral naltrexone administration in the early phase of alcohol withdrawal. METHODS Cortisol and adrenocorticotrophic hormone (ACTH) responses to naltrexone were measured in alcohol-dependent males (n=23) and in healthy males (n=20). Blood samples were collected for cortisol and ACTH measurements before administering (0 min) 50 mg naltrexone at 08.00 in the morning, and at 60, 90, 120 and 180 min after administering naltrexone. RESULTS Naltrexone administration resulted in a significant ACTH response in the patients while cortisol and ACTH responses were found to be significant in the controls. Cortisol response was not large enough to reach significance in the patients. ACTH level changes as a response to naltrexone in the patients were lower than that in the controls. DISCUSSION The study revealed blunted cortisol and attenuated ACTH responses to naltrexone in early alcohol withdrawal. This study may have shown impairment in adrenal and pituitary levels during alcohol withdrawal.