Selcuk Kirli

Effects of long-term antidepressant treatment on oxidative status in major depressive disorder: A 24-week follow-up study

PURPOSE Major depressive disorder (MDD) is a devastating disease that afflicts large populations and has also been accepted to be an independent risk factor for cardiovascular disease (CVD). Oxidative stress seems to play an essential role in the relationship of MDD and CVD. We aimed to determine the level of oxidative stress in patients with MDD and to investigate the effects of long-term antidepressant (AD) treatment on the oxidative-antioxidative system parameters and CVD risk factors. METHOD Fifty patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for MDD and 44 healthy control subjects were included in the study. Control visits of the patients were repeated 6weeks, 12weeks and 24weeks after beginning of the AD treatment. Lipid profiles, oxidation and oxidizability of apolipoprotein B-containing lipoproteins (expressed as apo B-b-MDA and apo B-Δ-MDA, respectively), levels of plasma malondialdehyde (p-MDA), total antioxidative capacity (TAOC), antioxidant molecules and antioxidant enzyme activities including paraoxonase/arylesterase, red blood cell superoxide dismutase (RBC-SOD) and glutathione peroxidase were determined during 24-week of follow-up period. RESULTS According to the results of the study, p-MDA, apo B-b-MDA and RBC-SOD activity were increased and arylesterase activity was decreased in MDD patients. Body mass index (BMI), vitamin A and total cholesterol levels in MDD patients increased after 24-weeks of AD treatment. RBC-SOD activity, TAOC, p-MDA and apo B-b-MDA levels were decreased; paraoxonase/arylesterase activities and apo B-Δ-MDA were increased at the end of 24th week. CONCLUSION Oxidative stress, demonstrated in MDD patients, was partly improved during 24weeks of AD treatment. Increase in paraoxonase/arylesterase activities and decrease in p-MDA and apo B-b-MDA levels after 24weeks seem to be beneficial for reduction of CVD risk in MDD patients. However increased BMI and apo B-Δ-MDA levels are negative cardiovascular effects of long-term AD treatment.

Oxidative-antioxidative systems and their relation with serum S100 B levels in patients with schizophrenia: effects of short term antipsychotic treatment.

Oxidative stress may be a contributing factor in the etiopathophysiology of schizophrenia, which may be exacerbated by the treatment with antipsychotics with pro-oxidant properties. Increased levels of S100 B are associated with neurodegenerative disorders, including schizophrenia. The aim of the present study was to investigate the role of oxidative cell damage in the pathogenesis of schizophrenia. Forty patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia and 35 healthy control subjects were included in the study. Serum S100 B level was determined to investigate brain damage. Plasma malondialdehyde (MDA) levels and susceptibility of red blood cell (RBC) to oxidation were determined to investigate the oxidative status and plasma vitamin E, vitamin C, serum total carotenoid levels and total antioxidant capacity and RBC superoxide dismutase (SOD) and whole blood glutathione peroxidase activities were measured to investigate the antioxidative defence before and after 6 weeks of antipsychotic treatment. Plasma MDA and serum S100 B levels and RBC-SOD activity were significantly higher in the schizophrenia group than those of the control group. Treatment did not modify any of the oxidative-antioxidative system parameters or serum S100 B levels. S100 B level was significantly higher in patients with negative symptoms than the patients with positive symptoms and the control subjects. S100 B levels were significantly reduced after 6 weeks of treatment in patients with negative symptoms. The results of the present study might support the oxidative cell injury hypothesis of the schizophrenia. Furthermore, the underlying mechanisms of the subgroups of schizophrenia might be different as suggested by the increased S100 B levels and its decrement after treatment in patients with negative symptoms.

The impact of ω-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: An open-label pilot study

Classical antipsychotics like haloperidol are suggested to increase oxidative stress and oxidative cell injury in the brain. Pro-oxidant effect of haloperidol may influence the course and treatment outcomes of schizophrenia. Dietary supplementation of either antioxidants or omega-3 fatty acids was found to improve symptoms of schizophrenia. Thus we decided to assess the impact of combining omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol. Ongoing haloperidol treatment of 17 schizophrenia patients was supplemented with 1000 mg capsule of omega-3 fatty acids (180 mg EPA+120 mg DHA) bid, vitamin E 400 IU bid and vitamin C 1000 mg/day. Patients were assessed with Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), Simpson Angus Scale (SAS) and Barnes Akathisia Rating Scale (BARS) over a 4 month period. Gluthatione peroxidase, superoxide dismutase, malondialdehyde, vitamin E and C levels were also evaluated at baseline and at the end of study. BPRS, SANS, SAS and BARS scores obtained at follow-up visits were significantly lower compared to baseline. Superoxide dismutase level was significantly lower at the end of study. No significant differences were detected in other laboratory parameters. Our results support the beneficial effect of the supplementation on positive and negative symptoms of schizophrenia as well as the severity of side effects induced by haloperidol. The effect of supplementation on akathisia is especially noteworthy and it has not been investigated in previous studies.

Oxidation of apolipoprotein B-containing lipoproteins and serum paraoxonase/arylesterase activities in major depressive disorder

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.

A comparative study of sertraline versus imipramine in postpsychotic depressive disorder of schizophrenia

The objective of this study was to compare the efficacy and reliability of sertraline versus imipramine in the treatment of postpsychotic depressive disorder of schizophrenia. The diagnosis was based on DSM-IV research criteria. The Sympson-Angus Scale and SANS were performed in order to discriminate between depressive symptoms, the extrapyramidal side-effects of neuroleptics and the negative symptoms of schizophrenia. A 10-day placebo treatment period was applied to eliminate the possible influence of the placebo effect. The degree of severity of depression was determined using the Hamilton Depression Scale and the Clinical Global Impression Scale. The patients were randomly divided into two subgroups, each consisting of 20 people, who were given either 50 mg/day sertraline or 150 mg/day imipramine, and their progress was followed for 5 weeks. The diagnosis and treatment results were evaluated using the double-blind method. In conclusion, although both drugs were found to be effective, sertraline was found to be more advantageous than imipramine in terms of rapid onset of action; frequency, severity and duration of side-effects, and relapse risk of schizophrenia.

Coronary artery disease risk factors in patients with schizophrenia: effects of short term antipsychotic treatment

The aim of the present study was to investigate serum paraoxonase/arylesterase activities and oxidation/oxidizability of apolipoprotein B-containing lipoproteins and several coronary artery disease risk factors, including homocysteine, high sensitive C-reactive protein, tumour necrosis factor-α, leptin and adiponectin in patients with schizophrenia. Oxidation of lipoproteins plays an important role in atherogenesis, and the enzyme paraoxonase has been shown to prevent lipoprotein oxidation. Furthermore, low paraoxonase activity has been suggested to predict coronary artery disease. Forty patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia and 35 healthy control subjects were included in the study. Serum paraoxonase/arylesterase activities were determined spectrophotometrically. Malondialdehyde levels of apolipoprotein B-containing lipoproteins were determined before and after incubation with copper-sulphate, which yielded basal- and Δ-malondialdehyde values, respectively. Homocysteine and highly sensitive C-reactive protein levels were determined using a fluorescence-polarization immunoassay and immunonephelometry, respectively. Leptin and adiponectin levels were measured with radioimmunoassay and tumour necrosis factor-α was determined by enzyme linked immunosorbent assay. Serum paraoxonase and arylesterase activities were significantly lower and Δ-malondialdehyde levels were significantly higher in the schizophrenia group compared with the control group. However, there were not any significant differences in other parameters of the study between the study groups. There was a significant increase in body mass index and serum triglyceride and very low density lipoprotein cholesterol levels in the schizophrenic group after 6 weeks of treatment. These parameters were significantly increased in patients treated with atypical antipsychotics but not in patients treated with typic or long acting antipsychotics. The results of the present study suggest that patients with schizophrenia might have increased risk for coronary artery disease related to reduced serum paraoxonase activity and increased oxidizability of apolipoprotein B-containing lipoproteins.

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.

Reliability and validity of the Geriatric Depression Scale in detection of poststroke minor depression

Objective: The aim of this study was to assess the validity and reliability of the 30-item Geriatric Depression Scale (GDS) as a screening tool for minor depression in poststroke patients. Method : Literate patients older than 18 years of age, diagnosed to have stroke, were eligible for the study. Standardized Mini Mental Status Examination (S-MMSE) and GDS were applied to all patients. The GDS was readministered 7 days later for retest reliability. Results: A total of 85 participants—49 nondepressed and 36 with minor depression—were eligible for the study. Cronbachs alpha coefficient was .89 in internal consistency analysis. The GDS scores were significantly higher (p < .001) in the depressed participants reflecting a high discriminant validity. The highest sum of sensitivity and specificity values of 1.44 (sensitivity = .69, specificity = .75) and 1.45 (sensitivity = .66, specificity = .79) were obtained for cutoff scores of 10/11 and 11/12, respectively. The area under receiver operating characteristics curve was .82. The test–retest reliability analysis revealed a high Pearson correlation coefficient (r = .75). Conclusion: Our findings suggest that the 30-item GDS has high discriminant validity, internal consistency, and test–retest reliability and reasonably useful cutoff scores; thus it can be used as a screening tool for minor depression in the poststroke population.

Hyperprolactinemia and possibly related development of prolactinoma during amisulpride treatment; three cases

Abstract Schizophrenia is a chronic and debilitating psychotic mental disorder that affects about 1% of the worlds population. Antipsychotic drugs are the mainstay of treatment in schizophrenia. Hyperprolactinemia, which is a common side effect of typical antipsychotics, is also associated with the use of some of the newer atypical agents. Antipsychotics may enhance prolactinoma growth as manifested by an increase in serum prolactin concentration. Prolactin-secreting pituitary adenomas possibly related with antipsychotics have been described in the literature. To our knowledge, this is the first series of cases showing a possible relation between pituitary adenomas and amisulpride treatment in patients with schizophrenia.

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.