Ralf Uebelhack

Black cohosh and St. John's wort for climacteric complaints: a randomized trial.

OBJECTIVE: To investigate the efficacy of the fixed combination of black cohosh (Cimicifuga racemosa) and St. John’s wort (Hypericum perforatum) extracts in women with climacteric complaints with a pronounced psychological component. METHODS: In this double-blind randomized placebo-control study, 301 women experiencing climacteric complaints with psychological symptoms were treated with ethanolic St. John’s wort extract and isopropanolic black cohosh extract or a matched placebo for 16 weeks. Climacteric complaints were evaluated by means of the Menopause Rating Scale mean score, and psychological complaints were evaluated using the Hamilton Depression Rating Scale sum score. RESULTS: The mean (± standard deviation) Menopause Rating Scale score decreased 50% (0.46 ± 0.13 to 0.23 ± 0.13) in the treatment group and 19.6% (0.46 ± 0.14 to 0.37 ± 0.15) in the placebo group. The Hamilton Depression Rating Scale total score decreased 41.8% in the treatment group (18.9 ± 2.2 to 11.0 ± 3.8 points), and 12.7% in the placebo group (18.9 ± 2.1 to 16.5 ± 4.3). The treatment was significantly (P < .001) superior to placebo in both measures. There were no relevant group differences regarding adverse events, laboratory values, or tolerability. CONCLUSION: This fixed combination of black cohosh and St. John’s wort is superior to placebo in alleviating climacteric complaints, including the related psychological component. LEVEL OF EVIDENCE: I

Imaging of serotonin transporters and its blockade by citalopram in patients with major depression using a novel SPECT ligand [123I]-ADAM

Summary.We studied the midbrain SERT availability in patients with major depression and assessed the relation of SERT occupancy by citalopram to the treatment response. 21 non-medicated patients with major depression and 13 healthy controls were examined by [123I]-ADAM SPECT. The midbrain SERT availability (SERT V3″) was calculated using individual MRI scans. In 13/21 patients SPECT was repeated 7 days after oral medication with citalopram (10 mg/day). We found no significant difference in the mean midbrain SERT availability between the studied patients with major depression and healthy controls (0.86 ± 0.27 vs. 0.71 ± 0.44, p = 0.069). The mean SERT occupancy accounted to 61%. The degree of SERT blockade by citalopram did not correlate with the reduction in HAMD total score. Treatment with low-dosed citalopram caused individually variable occupancy of the midbrain-SERT and a rapid clinical improvement in 54% of the investigated patients.

Peripheral serotonergic markers in acutely suicidal patients. 1. Comparison of serotonergic platelet measures between suicidal individuals, nonsuicidal patients with major depression and healthy subjects

SummaryBackground. A robust association between “suicidality” and deficits of the serotoninergic neurotransmission has been claimed in the past. However, many studies having investigated the relationship between suicidality and peripheral indicators of serotoninergic neurotransmission suffer from considering only one or a very small number of potentially useful serotoninergic parameters, whereas a synoptic multidimensional approach appears to be more appropriate. Furthermore, the psychiatric context within which suicidal behaviour occurs should be considered when interpreting biochemical findings of patients with suicidal ideation and suicide attempts. Methods. In the present study 5 peripheral serotonergic markers, (platelet 5HT concentration, 5HT uptake activity, 5HT2A receptor binding characteristics, MAO-B activity and tryptophan concentration in plasma) were assessed simultaneously. Of the 60 acutely suicidal inpatients (ICD-10: F43.xx, n = 52; F31/32/33, n = 8), 45 were suicide attempters. Data of 28 nonsuicidal patients with major depression (F31, n = 4; F32, n = 14; F33, n = 10) and 123 healthy volunteers represented the control groups. Results. Mean platelet 5HT concentration was significantly lower in suicidal inpatients when compared to nonsuicidal depressed patients, but did not differ from the figure in healthy subjects. Nonsuicidal depressed patients showed significantly higher mean platelet-5HT concentration than healthy controls.Mean Vmax of 5HT uptake in washed platelets, but not in platelet-rich plasma, was significantly higher in suicidal patients than in healthy controls, not, however, when compared to nonsuicidal depressed patients.Mean KD for the platelet 5HT2A receptor and MAO-B activity were significantly lower in suicidal patients as compared to nonsuicidal depressed patients and healthy controls.The observed differences in peripheral serotonergic markers between groups are partially due to a significant gender effect. A lower MAO-B activity was observed only in suicidal females, while the higher Vmax of 5HT uptake in washed platelets of suicidal patients was due to suicidal males. Conclusions. In view of conflicting observations made by other authors and the present findings on suicidal patients with adjustment disorder it remains doubtful whether and if so to which extent platelet studies can provide valid information on serotonergic mechanisms related to suicidal behaviour.

Functional motor asymmetries correlated with clinical findings in unmedicated schizophrenic patients

SummaryMotor asymmetries were investigated in 28 unmedicated schizophrenic in-patients and 32 healthy controls. Of the patients, who were assessed as righthanders by a handedness questionnaire, 46.4% changed their motor laterality in at least one part of the tapping test series, probably because of a decrease of functional hemispheric asymmetry. These patients were characterized by more pronounced psychotic symptoms than those who did not change motor laterality. According to the tapping frequency, two groups of patients could be distinguished: the high-and the low-frequency group. In both groups certain tapping data could be correlated with characteristic clinical features. While the findings in the high-frequency group point to an enhanced activation level of the right hemisphere and appear to be correlated with the onset of positive symptoms and better prognosis, the findings in the low-frequency group may be a reflection of a disturbed function of the left frontal region and seem to be correlated with a gradual chronic development of predominant negative symptoms with worse prognostic implications.

Effects of Cactus Fiber on the Excretion of Dietary Fat in Healthy Subjects: A Double Blind, Randomized, Placebo-Controlled, Crossover Clinical Investigation

Background Cactus (Opuntia ficus-indica) fiber was shown to promote weight loss in a 3-month clinical investigation. As demonstrated by in vitro studies, cactus fiber binds to dietary fat and its use results in reduced absorption, which in turn leads to reduced energy absorption and ultimately the reduction of body weight. Objective The objective of our study was to elucidate the dietary fat binding capacity of cactus fiber through determination of fecal fat excretion in healthy volunteers. Subjects and Methods This clinical investigation was performed as a double-blind, randomized, placebo-controlled, crossover study in healthy subjects for a period of approximately 45 days. Twenty healthy volunteer subjects were randomized to receive cactus fiber or placebo, 2 tablets thrice daily with main meals. All subjects were provided with meals during the study period (except washout) according to a standardized meal plan, with 35% of daily energy need coming from fat. Two 24-hour feces samples were collected during both the baseline and treatment periods for analysis of the fat content. Results Cactus fiber showed an increased fecal fat excretion compared with placebo (mean [SD] = 15.79% [5.79%] vs 4.56% [3.09%]; P < 0.001). No adverse events were reported throughout the study period. Conclusions Cactus fiber has been shown to significantly promote fecal fat excretion in healthy adults. The results of our study support the hypothesis that cactus fiber helps in reducing body weight by binding to dietary fat and increasing its excretion, thus reducing dietary fat available for absorption. ClinicalTrials.gov identifier: NCT01590667.

Aromatic amino acids in weight-recovered females with anorexia nervosa.

OBJECTIVE Most previous studies investigating amino acid levels in anorexia nervosa (AN) have focused on acutely underweight patients. The present study assessed the availability of aromatic amino acids in the plasma of weight-recovered outpatients with AN (recAN) in comparison to acutely underweight AN patients (acAN) and healthy control woman (HCW). METHOD Plasma tryptophan (TRP), tyrosine (TYR), and phenylalanine (PHEN) as well as leptin concentration were determined in 32 recAN, 32 acAN, and 32 HCW. RESULTS Both recAN and acAN patients showed significantly lower levels of TRP and PHEN when compared to HCW. TYR was reduced in acAN patients only. DISCUSSION Normal weight and normal leptin levels but lower availability of TRP and PHEN in recAN patients might indicate that outside a tightly controlled setting these patients still engage in abnormal eating patterns. Reduced peripheral availability of these precursor amino acids could impact on 5-HT and catecholamine functioning in the brain.

Three Cases of Successful Tryptophan Add-On or Monotherapy of Hepatitis C and IFNα-Associated Mood Disorders

BACKGROUND Interferon-alpha (IFN(alpha))-associated mood disorder is a major complication of treatment for chronic hepatitis C. METHOD The authors report on three patients infected with chronic hepatitis C showing severe depressive symptoms during or after IFN(alpha) treatment. Because patients had lowered tryptophan blood levels and did not response to antidepressants, they received tryptophan up to a dosage of 1,000 mg/day as mono- or add-on treatment. RESULTS Tryptophan, used as augmentation or monotherapeutic treatment, led to a significant improvement of depressive symptoms in all three patients. CONCLUSION A tryptophan deficit seems to be involved in the pathophysiology of persistent mood changes during and after IFN(alpha) treatment.

S100B in underweight and weight-recovered patients with anorexia nervosa.

Anorexia nervosa (AN) commonly arises during adolescence, leading to interruptions of somatic and psychological development as well as to cortical atrophy and reductions of brain volume. While most brain changes shift towards normal with weight restoration, it is not certain whether they are related to the loss of brain cells, neuropil or merely due to fluid shifts. We measured S100B serum concentrations and psychometric characteristics in 34 patients with acute AN, 19 weight-recovered patients and 35 healthy control women (HCW). Plasma tryptophan and leptin levels were determined as markers for malnutrition and neuroendocrine adaptation to semi-starvation. Peripheral S100B concentrations of acute and former AN patients were not elevated and not statistically different from HCW. BMI, peripheral leptin levels and measures of psychopathology as well as executive cognitive functioning did not correlate with S100B. Plasma tryptophan was positively related to S100B. Our results are in line with our previous findings showing unaltered GFAP and NSE plasma levels in patients with acute AN. Together they do not support hypotheses comprising the degeneration of glial or neuronal cells to explain common signs of brain atrophy in patients with acute AN.

Platelet Monoamine Oxidase Activity in Underweight and Weight-Recovered Females with Anorexia Nervosa

INTRODUCTION Central serotonergic pathways may play an important role in the etiology of anorexia nervosa (AN). Although platelet monoamine oxidase activity (MAO-B) has been proposed as an index of cerebral serotonin activity, studies in patients with AN are scarce. METHODS Platelet MAO-B activity was determined in 59 acutely underweight AN patients (acAN, aged 14-29 years, BMI=15.2+/-1.4), 35 weight-recovered AN patients (recAN, aged 15-29, BMI=20.8+/-2.2) and 59 healthy control women (HCW, aged 14-26, BMI=21.6+/-2.1). Plasma leptin served as an indicator of malnutrition. Results were compared by ANCOVA controlling for confounding variables. RESULTS Platelet MAO-B activity in acAN patients (5.2+/-1.4 nmol/10 (9)pltx15 min) was similar to HCW (5.5+/-1.9) but significantly lower in recAN patients (4.4+/-1.5). BMI and leptin showed a significant negative correlation with MAO-B activity in AN patients, but not in HCW. DISCUSSION Our results highlight the importance of malnutrition for the interpretation of abnormalities in neurotransmitter systems in AN. Whether low MAO-B activity in weight-recovered AN patients indicates a premorbid trait or a secondary change due to recovery remains to be elucidated.

A Review of the Efficacy and Safety of Litramine IQP-G-002AS, an Opuntia ficus-indica Derived Fiber for Weight Management

Sedentary lifestyle and caloric overconsumption are the key determinants of the escalating obesity prevalence. Reducing dietary fat absorption may help to induce a negative energy balance and thus help in managing weight problem. Apart from approved drug therapies, weight problems may also be aided with alternative and natural treatments. This paper compiled and reviewed the efficacy and safety of Litramine IQP-G-002AS, an Opuntia ficus-indica (OFI) derived fiber, in reducing dietary fat absorption and promoting weight loss. Evidence reviewed shows that Litramine IQP-G-002AS displays efficacy in promoting fat excretion and weight loss in four randomized, placebo-controlled clinical studies (including an unpublished pilot study). With a daily dosage of 3 g over a seven-day period, Litramine IQP-G-002AS showed an increased faecal fat excretion compared with placebo (15.8% (SD 5.8%) versus 4.6% (SD 3.1%); P < 0.001). In a 12-week study, significant greater weight loss (3.8 kg (SD 1.8 kg) versus 1.4 kg (SD 2.6 kg); P < 0.001) was observed in overweight and obese subjects treated with Litramine IQP-G-002AS as compared to placebo. No relevant gastrointestinal side effects have been reported for Litramine IQP-G-002AS at the dosages studied.