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Biomedical subjects

B Bandelow

Publications and source records attributed to B Bandelow.

At least 19 recordsLinked to original sources

Rgs 2 gene polymorphisms as modulators of anxiety in humans?

Rgs2 (regulator of G-protein signalling 2) gene recently was reported as a quantitative trait gene for anxious behaviour in mice and male Rgs2 knockout mice have been shown to be more anxious than wildtype mice. Therefore we investigated four non-coding single nucleotide polymorphisms in a sample of 173 patients with panic disorder and 173 matched controls of German descent. At the genotype level all four SNPs were associated with panic disorder (p = 0.02-0.05). At the haplotype level the strongest association was observed for a haplotype containing SNP3 and SNP 4 (subgroup men and men with agoraphobia: p = 0.01 and 0.03). This points towards a functional polymorphism at the 3' end of the gene. Our results support the hypothesis that variations of the Rgs2 gene play a role also for the development of anxiety in humans.

Agoraphobia↗

[The alpha2delta subunit of the voltage-dependent calcium channel. A new pharmaceutical target for psychiatry and neurology].

Calcium channel blockers are substances used for treating high blood pressure and coronary heart disease. New medications have been developed that modulate calcium channels but also show promise in psychiatric and neurologic applications. Gabapentin and pregabalin bind to a subunit of calcium channels--the alpha2delta receptors--thereby reducing calcium influx to neurons. As a result, less glutamate is released from nerve endings that use excitatory amino acids as transmitters. This in turn reduces substance P-related activation of AMPA heteroreceptors on noradrenergic synapses, total transmitter release, and finally neuronal activity. That mechanism is the probable explanation for gabapentin's and pregabalin's usefulness in the treatment of neuropathic pain but also their possible anticonvulsive and anxiolytic effects.

Animals↗

[Pharmacotherapy in personality disorders].

Subjects with personality disorders represent a relevant subset of the clinical psychiatric population and, to an even bigger extent, a comorbid condition to an axis-I diagnosis. Personality disorders appear to be difficult to treat and problematic in the therapeutic setting, and a pharmacologic treatment often does not follow recommendations from empirical studies. Psychopharmacologic drugs are able to modify the expression of certain personality dimensions, which are mainly disorder-related variables of temperament. Modern pharmacotherapy of personality disorders has a neurobiological basis. This is underlined by evidence from animal studies and can be associated with certain receptor-specific functions in humans. Treatment is consequently symptom-related and not specific for any disorder. It must be stressed that certain features but not the entire personality can be modified by drug treatment. Data from drug studies are still relatively scarce. An overview of studies on personality disorders is presented including information on dosages and augmenting strategies. Psychotherapy still is the basic treatment for personality disorders. However, psychopharmacological interventions should not only be considered when psychotherapy has failed. Treatments should be complementary from the start. There is a rationale for short- and long-term treatment. The latter is indicated, despite of the scarcity of data, when longer lasting and severe affective symptoms emerge. Response rates vary among the trials and appear to be lower than in non-comorbid axis-I disorders. A treatment algorithm is presented.

Anticonvulsants↗

Randomized, double-blind study of SR142801 (Osanetant). A novel neurokinin-3 (NK3) receptor antagonist in panic disorder with pre- and posttreatment cholecystokinin tetrapeptide (CCK-4) challenges.

OBJECTIVE: The present study was designed to examine the efficacy and tolerability of the non-peptide neurokinin-3 (NK3) receptor antagonist SR142801 in outpatients suffering from panic disorder. METHODS: In a pilot study, 52 patients who were responders to a cholecystokinin tetrapeptide (CCK-4) challenge were randomized to four weeks of treatment with SR142801 (n = 36) or placebo (n = 16). Panic symptoms were assessed on weekly visits and a second CCK-4 challenge was performed at the end of the double-blind placebo controlled treatment period. Tolerability of SR142801 was generally good. RESULTS: The proportion of patients who had at least one adverse event (AE) in the SR142801 group and the placebo group was similar (58.3 and 50 %, respectively). Independent of treatment group, patients' overall panic symptomatology was substantially improved at the end of the treatment. CONCLUSION: With regard to efficacy of outcome, the compound was not significantly different from placebo. However, post-CCK-4 plasma prolactin concentrations showed a significant difference between placebo and SR142801.

Adolescent↗

Randomized double blind comparison of olanzapine vs. clozapine on subjective well-being and clinical outcome in patients with schizophrenia.

OBJECTIVE: This randomized double-blind multicenter trial evaluated the effects of olanzapine vs. clozapine on subjective well-being, quality of life (QOL) and clinical outcome. METHOD: The primary objective was to demonstrate non-inferiority of olanzapine, mean dosage 16.2 +/- 4.8 (5-25 mg/day) vs. clozapine, mean dosage 209 +/- 91 (100-400 mg/day) regarding improvement on the 'Subjective Well-Being under Neuroleptic Treatment' (SWN) Scale after 26 treatment weeks in 114 patients with schizophrenia. Secondary outcome parameters included: Munich QOL Dimension List (MLDL), Positive and Negative Symptom Scale (PANSS), Clinical Global Impression (CGI). RESULTS: SWN scores improved significantly in both groups, olanzapine was non-inferior to clozapine (group difference 3.2 points in favor of olanzapine; 95% CI: 4.2;10.5). MLDL-satisfaction, PANSS and CGI-S improved similarly, olanzapine yielded a higher CGI Therapeutic Index. Individual SWN and PANSS changes correlated only moderately (r = -0.45). CONCLUSION: Olanzapine was non-inferior to clozapine. The lack of a marked correlation between PANSS and SWN improvements indicates that patients and psychiatrists perceive treatment differently.

Adolescent↗

[Anxiety-ridden patients in the doctor's office].

Initially, patients with anxiety syndromes consult the general practitioner complaining of physical symptoms. After an appropriate differential diagnostic work-up, the family doctor can therefore check whether the patient might possibly be suffering from an anxiety disorder. For the treatment of such disorders, psychotherapeutic and psychopharmacological strategies all have a role to play. The general practitioner can initiate supportive medication before referring the patient to a specialist. Early detection and treatment of an anxiety disorder can prevent the condition from becoming chronic and may also obviate the need for unnecessary repeated diagnostic measures and treatments.

Agoraphobia↗

Blood dyscrasias induced by psychotropic drugs.

Drugs can cause a variety of blood dyscrasias, e. g., by interfering with hematopoiesis in the bone marrow or damaging mature blood cells by antibodies. Although numerous reports on the risks of adverse hematological effects associated with psychotropic drugs have led to stringent monitoring requirements for some compounds, particularly neuroleptics, it is still difficult to estimate the true prevalence of such risks. Sixteen episodes of thrombocytopenia, 63 of neutropenia, 22 of agranulocytosis, 4 episodes of severe neutro- and thrombocytopenia, and 2 of pancytopenia were documented by the drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) in a population of 122,562 patients between 1993 and 2000. All cases were related to the epidemiological data provided for this population and systematically analyzed as regards history of medication, co-medication, and the clinical course. Putative risk rates for the main groups of medications and a number of drugs could be estimated with this database. Most changes in the white blood cell counts, which were rated as probably or definitely drug-induced, were attributed to clozapine (0.18 % of patients exposed), carbamazepine (0.14 %) and perazine (0.09 %). In patients on newer atypical neuroleptics, we documented neutropenia assumed to be probably or definitely drug-related in five patients during treatment with olanzapine and in one case with risperidone. In all five olanzapine-related cases, the drugs were the sole cause of the adverse drug reactions. All surveyed patients who received clozapine showed no difference in age and gender distribution from those who developed hematological changes. Incidences of hematological changes for antidepressants were much lower (about 0.01 %). Although the methodological accuracy of these findings has to be critically discussed these data could be of considerable clinical relevance and should be helpful in making clinical treatment decisions.

Adult↗

Hyperhomocysteinemia as a new risk factor for brain shrinkage in patients with alcoholism.

Chronic alcohol consumption can induce brain atrophy, whereby the exact mechanism of brain damage in alcoholics remains unknown. There is evidence that chronic alcoholism is associated with hyperhomocysteinemia. Homocysteine is an excitatory amino acid which markedly enhances the vulnerability of neuronal cells to excitotoxic and oxidative injury in vitro and in vivo. The present volumetric magnetic resonance imaging study included 52 chronic alcoholics and 30 non-drinking healthy controls. Patients were active drinkers and had an established diagnosis of alcohol dependence. We investigated the influence of different variables on the hippocampal volume of patients suffering from chronic alcoholism. We observed that pathological raised levels of plasma homocysteine showed the most significant correlation to hippocampal volume reduction (P<0.001, multiple regression analysis). Raised plasma levels of homocysteine are associated with hippocampal (brain) atrophy in alcoholism.

Adult↗

5-HT1A responsivity in patients with panic disorder before and after treatment with aerobic exercise, clomipramine or placebo.

Blunted neuroendocrine and physiological responses to the selective 5-HT(1A) receptor agonist, ipsapirone, have been observed in patients with panic disorder and/or agoraphobia (PDA). In order to examine whether this hyporesponsiveness to ipsapirone is modified by pharmacological or non-pharmacological therapeutic interventions, challenges with an oral dose of ipsapirone (0.3 mg/kg) and placebo were performed in patients with PDA before and after 10 weeks of treatment with clomipramine, aerobic exercise and placebo. Before treatment, administration of ipsapirone was followed by significant increases of cortisol, anxiety and other psychopathological symptoms in comparison to the placebo challenge. In addition, a significant decrease of body temperature was observed. After the 10-week treatment period, the psychological responses to ipsapirone were significantly reduced in the clomipramine and the exercise group. In contrast, there was a non-significant trend towards higher cortisol responses after clomipramine and exercise treatment. The hypothermic response to ipsapirone was significantly reduced by clomipramine treatment. In conclusion, our results demonstrate that effective treatment of panic disorder has divergent effects on the psychological, neuroendocrine and temperature responses to ipsapirone.

Adolescent↗

[Behavior therapy and antidepressive drugs. What helps with anxiety?].

Up to 25% of patients seen in the doctor's office are suffering from some sort of anxiety disorder. In accordance with the ICD-10 classification, such disorders include panic disorders with or without agoraphobia, generalized anxiety disorders, social phobia, specific phobia and mixed forms comprising anxiety and depression. Comorbidity with other anxiety disorders and depression is common. Symptoms reported by affected patients may suggest organic disease, which first must be excluded. All patients with severe persistent anxiety states require psychotherapeutic measures (cognitive behavioral treatment, exposure treatment). Selective serotonin reuptake inhibitors are the medication of first choice in anxiety disorders and comorbid depression.

Antidepressive Agents↗

Smoking modulates neuroendocrine responses to ipsapirone in patients with panic disorder.

Reduced 5-HT1A-receptor responsiveness has been reported in patients with panic disorder(PD) and/or agoraphobia (PDA). Although many of these patients are regular smokers, it has not been examined whether psychological or neurobiological effects induced by the selective 5-HT1A-receptor agonist, ipsapirone, are affected by the smoking status of the patients. In order to clarify this question neuroendocrine challenges with oral doses of ipsapirone (0.3 mg/kg) and placebo were performed in 39 patients with PDA, and results were compared between patients who smoked (>10 cigarettes per day, n = 17) and patients who had been non-smokers for at least two years (n = 22). Patients who were smokers (but did not smoke during the challenge procedure) had significantly reduced baseline concentrations of cortisol and a significantly lower body temperature. In comparison to placebo, administration of ipsapirone was associated with significant increases of various psychological symptoms and plasma cortisol concentrations. The subgroup of PD patients who were smokers showed significantly higher cortisol responses to ipsapirone than non-smokers. In conclusion, smoking status has to be taken into account when assessing the responsiveness of 5-HT1A receptors in patients with psychiatric disorders. The prevention of smoking during challenge sessions might not be the ideal approach in heavy smokers, since sudden abstinence from smoking is likely to affect neurobiological and possibly psychological responses to ipsapirone.

Adult↗

Clozapine-associated elevation of plasma cholinesterase.

OBJECTIVE: The goal of this study was to identify adverse effects of the atypical neuroleptic clozapine on liver function and lipid metabolism. METHODS: Data which included serum levels of clozapine and its hepatic metabolite N-desmethyl clozapine were collected from medical records of patients treated with clozapine and controls. RESULTS: We identified a clozapine-associated marked elevation of plasma cholinesterase (ChE) with unchanged levels of AST, ALT or g-GT. ChE was correlated to the serum level of clozapine and even closer to N-desmethyl clozapine. For the total patient group we observed significant correlations of ChE with the body-mass index and body weight. However, clozapine-treated patients and controls did not differ with regard to body-mass index, triglycerides, and cholesterol. CONCLUSION: We report for the first time a clozapine-associated and dose-dependent elevation of plasma ChE, which may be related to clozapine-associated effects on hepatic lipid metabolism or ChE enzyme induction.

Adult↗

Effect of aerobic exercise on behavioral and neuroendocrine responses to meta-chlorophenylpiperazine and to ipsapirone in untrained healthy subjects.

RATIONALE: Several clinical studies suggest antidepressive and anxiolytic effects of regular aerobic exercise. OBJECTIVES: The present study examines the effects of a 10-week protocol of moderate aerobic exercise (3-4 miles jogging 3 times per week) on central serotonergic receptor sensitivity. METHODS: Neuroendocrine challenges using oral doses of meta-chlorophenylpiperazine (m-CPP; 0.4 mg/kg), ipsapirone (0.3 mg/kg), and placebo were performed in 12 untrained healthy volunteers before and after 10 weeks of moderate aerobic exercise. RESULTS: Before training, administration of the non-selective serotonergic agonist m-CPP, which exerts a number of well-reproducible effects mainly via its action on 5-HT2C receptors, was associated with a significant increase of cortisol and prolactin (but not adrenaline or noradrenaline) in comparison with the placebo condition. After the 10-week training period, administration of m-CPP was followed by a blunted cortisol response which was not significantly increased in comparison to the placebo challenge. In contrast, the increases of cortisol observed after administration of the 5-HT1A agonist ipsapirone were of the same magnitude during the pre- and post-training challenge sessions. The behavioral response to ipsapirone and the mean maximal increases of plasma adrenaline and noradrenaline did not change during the training period. CONCLUSIONS: Regular aerobic exercise is associated with a blunted cortisol response to m-CPP, which might reflect a downregulation of central 5-HT2C receptors.

Adult↗

Separation anxiety and actual separation experiences during childhood in patients with panic disorder.

OBJECTIVE: The association between separation anxiety in childhood and actual separation experiences during childhood has not yet been investigated in patients with panic disorder. METHODS: In 115 patients with panic disorder with or without agoraphobia and in 124 control subjects without a history of psychiatric illness, we assessed separation anxiety during childhood, retrospectively, using DSM-IV and ICD-10 criteria and the Separation Anxiety Symptom Inventory (SASI). In addition, actual separation experiences from age 0 to 15 years were assessed, retrospectively. RESULTS: A total of 22.6% of the patients and 4.8% of the control subjects fulfilled both DSM-IV and ICD-10 criteria for childhood separation anxiety (chi 2 = 11.8; P < 0.0001). Further, 57.4% of the patients and 37.9% of the control subjects reported actual separation experiences during their childhood (chi 2 = 9.09, P < 0.003). Separation anxiety and actual separation experiences, however, were independent of each other. CONCLUSION: These results suggest that separation anxiety during childhood is not a consequence of actual traumatic separation experiences in panic disorder patients.

Adolescent↗

[Cortisol in night-urine: Introduction of a research method in psychoneuroendocrinology].

Cortisol is one of the major parameters investigated in psychoneuroendocrinological research, but the methods employed for sample collecting are often unsatisfactory. A suitable method of sample collection should allow for the integrative assessment of long-term changes of the HPA-system, should be non-invasive, and should not exceed the subject's compliance. The assessment of cortisol in night-urine fulfils these demands; although this method has been occasionally employed, it has not yet been described systematically. For the first time a detailed description is given here that allows for a standardized replication. In ten previous studies and three investigations of our own this method has been successfully applied to detect changes in the cortisol excretion of patients with endocrinological and psychiatric disorders as well as in subjects under conditions of psychosocial stress. The determination of cortisol in night-urine represents an ideal method for the assessment of changes in the basal HPA-activity in numerous areas of psychoneuroendocrinological research, e.g. field and screening studies in natural environment, clinical studies in psychiatry and especially follow-up studies in psychotherapy research.

Adult↗

[Generalized anxiety disorders (GAD)--a neglected illness? Background und aims of the GAD-P study].

In the past Generalized anxiety disorder (GAD)--previously classified as anxiety neurosis--was regarded as not being a separate diagnostic entity. On the basis of new explicit criteria for GAD in the 90ies, GAD-specific pharmacological (i.e. SNRI) and psychological treatments with improved efficacy have become available. The Generalized Anxiety and Depression in Primary care study (GAD-P) investigates the prevalence of GAD in primary care settings and evaluates the patterns of care provided. Aims, methods and findings of the GAD-P study are described in this supplement.

Anti-Anxiety Agents↗

[Etiology of initially unexplained confusion of excitability in deadly nightshade poisoning with suicidal intent. Symptoms, differential diagnosis, toxicology and physostigmine therapy of anticholinergic syndrome].

HISTORY AND ADMISSION FINDINGS: After a walk in a wood a 55-year-old teacher was admitted to the emergency unit of a university hospital because of somnolence and excitability. Her rectal temperature was 37.8 degrees C, she had sinus tachycardia (rate of 130/min) but no other significant findings. INVESTIGATIONS: With the exception of C-reactive protein (10 mg/dl), MCV (101 fl), MCH (34 pg) and arterial blood gases (pH 7.483, pCO2 35.5 mmHg, base excess 5.1 mmp/l) laboratory tests were within normal limits. Qualitative screening of serum for benzodiazepines, barbiturates and antidepressives was negative. Neurological examination, including lumbar puncture and cranial computed tomography were noncontributory. TREATMENT AND COURSE: 10 hours after admission the patient developed signs of an anticholinergic syndrome with mydriasis, dry mouth, tachycardia, hot skin and an atonic bladder. Physostigmine 2 mg completely reversed the neurological and mental symptoms. After gas chromatography, mass-spectrometry of a urine sample showed an atropine molecular fragment with a molecular weight of 271. At intervals of 3 to 5 hours the recurrence of confusion and excitability required 4 further i.v. injection of physostigmine. The patient subsequently became accessible to psychiatric examination and reported that during the walk she had swallowed 8-10 berries of deadly nightshade with suicidal intent. CONCLUSION: In case of excitability and confusion as well as somnolence or coma of uncertain aetiology an anticholinergic syndrome caused by ingestion of atropine-containing plants or psychoactive drugs (phenothiazines, butyrophenones, tri- or tetracyclic antidepressants) should be included in the differential diagnosis. If there are suggestive clinical findings (tachycardia, somnolence, coma or threatened respiratory arrest, physostigmine should be given if there are no contraindications.

Akathisia, Drug-Induced↗