Managing reboxetine-associated urinary hesitancy in a patient with major depressive disorder: a case study.
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Adrenergic Uptake Inhibitors↗
Biomedical subjects
S Kasper
Publications and source records attributed to S Kasper.
[St. John's wort extract WS 5572 in minor to moderately severe depression. Effectiveness and tolerance of 600 and 1200 mg active ingredient daily].
BACKGROUND AND METHOD: In this multi-centre study, the effectiveness and tolerability of an extract of herba hyperici WS 5572 were examined. The total of 2,166 participating patients, all suffering from mild to moderate depression, were prescribed to take 600 mg (one tablet) or 1,200 mg (two tablets) daily. Four-hundred-forty-six general practitioners, psychiatrists and neurologists conducted the survey. Three quarters of the participating patients were female at an average age of 50 years. Most of the patients suffered from a depression which was diagnosed for the first time. Approximately in one third of the patients, a recurrent depression was diagnosed. RESULTS: The average severity of the depression was "moderate" (basing on CGI; Clinical Global Impression Scale) at the beginning of the survey and was reduced to less than "mild" after an average observation time of seven weeks. 83.7% patients (600 mg) and 88.6% (1,200 mg) responded respectively. During this observation period, an improvement in symptoms, measured in 17 items, was of clinical relevance. The treating physicians described the drug tolerance as being good or very good for 99% in all cases. This observation was confirmed by adverse drug reactions, which amounted to 0.41%. The low ratio of adverse drug reactions of 0.41% confirmed the physicians' judgement. CONCLUSION: The results obtained from this observational study were similar to those of an equally designed observation performed in 1998, where St. John's wort was observed in a dosage of 300 mg per tablet (standard dosage 3 x 300 mg/d). This is a good proof of the effectiveness and the tolerability of this drug in patients who are suffering from mild and moderate depressive episodes.
Depressive Disorder↗
[General practice research study of St. Johns Wort extract WS 5572. Normally 600 mg per day is enough].
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Clinical Trials as Topic↗
The effects of light therapy on mini-mental state examination scores in demented patients.
BACKGROUND: Preliminary evidence suggests that demented patients may experience beneficial effects of light therapy. The authors tested whether bright light therapy (BLT) is capable of improving cognitive functions in patients with Alzheimer-type dementia (AD) or vascular dementia (VD). METHODS: Twenty-three patients with AD or VD were randomly assigned to either evening BLT or dim light therapy (DLT). Effects of light therapy on cognitive functions were assessed before and after light therapy using Mini-Mental State Examination (MMSE) scores. Body temperature rhythm (BTR) was additionally recorded pre- and posttreatment. RESULTS: Irrespective of their diagnosis, patients treated with BLT (p =.0012) but not with DLT (p =.73) showed a statistically significant increase in MMSE total scores after light therapy. Evening BLT simultaneously induced a significant phase delay of 56 min on BTR (p =.025). CONCLUSION: Our preliminary results suggest that short-term evening BLT may exert beneficial effects on cognitive functioning in patients with dementia.
Aged↗
Use of the probasin promoter ARR2PB to express Bax in androgen receptor-positive prostate cancer cells.
BACKGROUND: Adenovirus-mediated overexpression of the apoptosis-inducing protein Bax can induce apoptosis in prostate cancer cell lines. Constitutive overexpression of Bax could result in unwanted apoptosis in every site of accidental Bax accumulation in vivo. Therefore, we developed an adenoviral construct (Av-ARR2PB-Bax) in which the probasin promoter, modified to contain two androgen response elements, drives Bax expression. This promoter would be expected to limit expression of Bax to cells expressing the androgen receptor. METHODS: A variety of androgen receptor (AR)-positive and -negative cell lines of prostatic or nonprostatic origin were infected with Av-ARR2PB-Bax or a control virus, Av-ARR2PB-CAT, in which the same promoter drives expression of the chloramphenicol acetyl transferase-reporter gene. Bax expression and apoptosis in vitro were assessed by western blot analysis. Tumor size and apoptosis in vivo were assessed after four weekly injections of Av-ARR2PB-Bax or Av-ARR2PB-CAT into subcutaneous LNCaP xenografts growing in uncastrated male mice. All statistical tests were two-sided. RESULTS: Bax was overexpressed in an androgen-dependent way in AR-positive cell lines of prostatic origin but not in AR-positive cells of nonprostatic origin or in AR-negative cell lines of either prostatic or nonprostatic origin. The androgen dihydrotestosterone activated apoptosis in LNCaP cells infected with Av-ARR2PB-Bax but not in those infected with Av-ARR2PB-CAT. Av-ARR2PB-Bax-injected LNCaP xenograft tumors decreased in tumor size from 34.1 mm3 (95% confidence interval [CI] = 25.1 mm3 to 43.1 mm3) to 24.6 mm3 (95% CI = -2.5 mm3 to 51.7 mm3), but the difference was not statistically significant (P =.5). Tumors injected with Av-ARR2PB-CAT increased in size, from 28.9 mm3 (95% CI = 12.7 mm3 to 45.1 mm3) to 206 mm3 (95% CI = 122 mm3 to 290 mm3) (P =.002) and contained statistically significant more apoptotic cells (23.3% [95% CI = 21.1% to 25.6%] versus 9.5% [95% CI = 8.0% to 11.1]) (P<.001). CONCLUSIONS: Av-ARR2PB-Bax induces androgen-dependent therapeutic apoptosis in vitro and in vivo by activating apoptosis in AR-positive cells derived specifically from prostatic epithelium and does not affect nonprostatic cells.
Adenoviridae↗
Strain-based sequence variations and structure analysis of murine prostate specific spermine binding protein using mass spectrometry.
Mouse spermine binding protein (SBP) has been characterized using mass spectrometry, including its localization within the prostate, sequence verification, and its posttranslational modifications. MALDI (matrix-assisted laser desorption/ionization) mass spectrometry was employed for localization of proteins expressed by different lobes of the mouse prostate obtained after tissue blotting on a polyethylene membrane. The mass spectra showed complex protein profiles that were different for each lobe of the prostate. The prostate-specific spermine binding protein (SBP), primarily identified by its in-source decay fragment ion signals, was found predominantly expressed by the ventral lobe of the prostate. The MALDI in-source decay measurements combined with nanoESI (nanoelectrospay ionization) MS/MS measurements obtained after specific proteolysis of SBP, allowed the exact positioning of a single N-linked carbohydrate group, and the identification of a pyroglutamate residue at the sequence N-terminus. The N-linked carbohydrate component was further investigated and the general pattern of the N-linked carbohydrate identified. The presence of a disulfide bridge between cysteine78 and cysteine124 was also established. The full sequence characterization of SBP showed several strain-based sequence differences when compared to the published gene sequence.
Amino Acid Sequence↗
No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism.
BACKGROUND: A polymorphism in the serotonin transporter promoter gene region (5-HTTLPR) has been shown to influence the quantity of serotonin transporter expressed in human cell lines: the 5-HTTLPR short allele (s) has been associated with reduced 5-HTT expression when compared to cells carrying the 5-HTTLPR long allele (l). We performed a single photon emission computed tomography (SPECT) study using the ligand [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT) to measure 5-HTT availability in 16 healthy subjects genotyped for 5-HTTLPR. METHODS: SPECT scans were performed 24 hours after tracer injection, regions of interest anatomically corresponding to the thalamus-hypothalamus and mesencephalon-pons areas were compared to the binding in the cerebellum, representing the nondisplaceable [(123)I]-beta-CIT-binding (results expressed as target activity minus cerebellum activity/cerebellum activity). DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods. RESULTS: Specific binding ratios in the thalamus-hypothalamus were 2.65 +/- 0.4 in subjects with the l/l genotype (n = 3), 2.76 +/- 0.5 in subjects with the l/s genotype (n = 9), and 2.77 +/- 0.4 in subjects with the s/s genotype (n = 4). Binding ratios in the mesencephalon-pons were 1.43 +/- 0.3 (l/l; n = 3), 1.37 +/- 0.3 (l/s; n = 9), and 1.28 +/- 0.3 (s/s; n = 4). None of these differences was statistically significant. CONCLUSIONS: Our data provide no evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects.
Adult↗
A probasin-large T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential.
Neuroendocrine (NE) cells may be involved not only in growth and differentiation of the normal prostate but also in carcinogenesis and progression of prostate adenocarcinoma (Pca), including development of androgen resistance. However, the exact pathophysiology of NE cells in Pca remains poorly understood. Here we describe a transgenic model of Pca with progressive NE differentiation. Seven lines of transgenic mice with the rat prostate-specific large probasin promoter linked to the SV40-large T antigen (Tag) that develop prostatic neoplasia have been established. In this study, one of the seven lines (12T-10) was characterized by examination of 52 mice aged from 2-12 months. With advancing age, low-grade prostatic intraepithelial neoplasia, high-grade prostatic intraepithelial neoplasia, microinvasion, invasive carcinoma, and poorly or undifferentiated carcinoma with NE differentiation appeared in the prostates in sequential order. Whereas Tag is expressed uniformly in prostate epithelium, only an increasing subset of cells in prostatic intraepithelial neoplasia showed NE differentiation by chromogranin immunostaining. Frankly invasive carcinoma developing subsequently showed occasional definitive glandular differentiation (adenocarcinoma) and particularly undifferentiated carcinoma with NE histological features similar to those observed in NE carcinomas in humans. The NE carcinomas occurred in the dorsolateral and ventral lobes and were generally androgen receptor negative. Twenty-one of 32 (66%) mice aged > or = 6 months and 15 of 17 (88%) mice aged > or = 9 months developed metastatic tumors, as confirmed by histology and/or Tag immunohistochemistry. Metastases occurred at the later time points, with metastasis to regional lymph nodes, liver, and lung being particularly common. Metastases showed histological features of NE differentiation, as confirmed by chromogranin immunostaining and electron microscopy. An athymic nude mouse that received a s.c. implant of a primary NE tumor developed Tag-positive metastatic tumors with similar NE differentiation. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry identified identical protein profiles between the primary NE tumor and lesions in the extraprostatic organs. Hence, in the 12T-10 large probasin promoter-Tag mouse, high-grade prostatic intraepithelial neoplasia develops progressively greater NE differentiation and progresses to invasive adenocarcinoma and NE carcinoma, with a high percentage of metastases. The predictable progression through these stages will allow testing of therapeutic interventions as well as possible further delineation of the role of NE cells in Pca progression.
Adenocarcinoma↗
[123I] beta-CIT and single photon emission computed tomography reveal reduced brain serotonin transporter availability in bulimia nervosa.
BACKGROUND: Impaired serotonin transmission has been implicated in the pathophysiology of eating disorders. We investigated the in vivo availability of brain serotonin transporters and dopamine transporters in bulimia nervosa patients. METHODS: Approximately 24 hours after injection of [123I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I] beta-CIT), single photon emission computed tomography scans were performed in 10 medication-free, female bulimic patients and 10 age-matched, healthy females. For quantification of brain serotonin transporter and dopamine transporter availability, a ratio of specific to nonspecific [123I] beta-CIT brain binding was used (V(3)" = target region - cerebellum/cerebellum). RESULTS: Drug-free bulimia nervosa patients showed a 17% reduced brain serotonin transporter availability in the hypothalamus and thalamus, as compared with healthy control subjects (2.4 +/- 0.4 vs. 2.9 +/- 0.4, p =.026), and a similar reduction in striatal dopamine transporter availability. There was a negative correlation of illness duration and serotonin transporter availability (r = -.65; p =.042) and a strong positive correlation between hypothalamic/thalamic and striatal V(3)" (r =.80, p <.001). CONCLUSIONS: This first report of reduced [123I] beta-CIT binding in a relatively small group of patients with bulimia nervosa suggests a reduced hypothalamic and thalamic serotonin transporter availability in bulimia, which is more pronounced with longer duration of illness.
Adolescent↗
[Recurrent brief depressive episodes. Epidemiology, clinical aspects, diagnosis and therapy].
Recurrent brief depression (RBD), an affective disorder with a similarly high risk of suicidal behavior as major depression (MD), is characterized by depressive episodes occurring about once a month that last only a few days. The combination of RBD and MD, called combined depression (CD), increases the risk of suicidal behavior enormously. Whereas patients with CD are usually in the care of psychiatrists or neurologists, epidemiological data demonstrate that RBD patients usually see only general practitioners and are not recognized as suffering from an affective disorder. Diagnostic criteria for RBD can be found in the ICD-10 and are helpful in both research and clinical routine. Recurrent brief psychiatric syndromes should be taken into differential diagnostic consideration and are discussed in detail in this review. However, the possibility of prospective diagnostic confirmation of RBD and the way of evaluating drug responses in prophylactic intervention of RBD differ essentially from those in treatment of MD and are more related to clinical procedures used in treating migraine or epilepsy. Differences in the courses of RBD and MD are responsible for different requirements in the design of drug treatment studies. Denial of special methodological needs and highly selected patient samples have probably been responsible for false negative results in double-blind, placebo-controlled treatment studies. Although several authors reported successful treatment of RBD with different compounds in about 60 patients, no treatment algorithm can be given. Future treatment studies without the limitations of previous studies are clearly needed in the field of RBD.
Antidepressive Agents↗
[Use of electroconvulsive therapy in psychiatry].
Electroconvulsive therapy (ECT) has antidepressive and antipsychotic effects. Since being introduced in Italy in 1938, its mode of action has still not been clarified. Treatment modalities have changed in many ways. ECT, in which a generalized epileptic seizure is provoked by electrical stimulation of the brain, is performed under short intravenous anesthesia and muscle relaxation. Considering careful previous clinical examination and anesthesiological and internal counterindications, ECT is a very safe form of treatment. Single cases of persisting memory impairment were described after the formerly common bilateral sinus wave stimulation. However, recent developments such as brief pulse stimulation, unilateral electrode placement, and individual stimulus titration (on the basis of EEG monitoring) make memory impairment as a consequence of ECT a rare event which mostly remits completely in 4-8 weeks. Today, ECT is performed mainly in patients suffering from severe, therapy-resistant affective or schizophrenic disorders. Pernicious catatonia and the neuroleptic malignant syndrome are emergency indications. Adequate ECT treatment requires a series of 6-12 individual sessions (every second or third day). In therapy-resistant depression, for which the greatest number of data are available, the response rate lies between 50 and 60%. This has been confirmed by a descriptive analysis of all ECT treatments at the Department of Psychiatry, University of Vienna, between 1994 and 2000. There is a need for controlled studies on continuation therapy subsequent to successful ECT.
Antipsychotic Agents↗
In vivo (123)I IBZM SPECT imaging of striatal dopamine 2 receptor occupancy in schizophrenic patients.
RATIONALE: Single photon emission computed tomography (SPECT) using (123)I iodobenzamide (IBZM) as tracer substance has been shown to be a useful tool to visualize dopamine 2 (D2) receptor occupancy. OBJECTIVES: We investigated the striatal D2 receptor occupancy of zotepine which is referred to the class of atypical antipsychotic drugs. METHODS: (123)I IBZM and SPECT were used to visualize striatal dopamine 2 (D2) receptor occupancy in zotepine-treated schizophrenic patients. Two groups of schizophrenic patients receiving either 150 mg/day zotepine (n=6) or 300 mg/day (n=6) underwent examination. For the quantification of striatal D2 receptor occupancy, striatal IBZM binding in patients treated with antipsychotics was compared to untreated healthy controls (n=8) reported earlier. RESULTS: Zotepine led to a mean overall striatal D2 receptor occupancy of 73%. Patients with 150 mg daily showed a significantly lower occupancy (65.8%, SD=6.2) than patients with 300 mg/day (77.8%, SD=10.7; P<0.05). No clinically relevant extrapyramidal side effects occurred during treatment with zotepine. CONCLUSIONS: There was no correlation between the degree of striatal D2 receptor occupancy and clinical improvement.
Adult↗
Prevalence of premenstrual dysphoric disorder in female patients with seasonal affective disorder.
BACKGROUND: Both seasonal affective disorder/winter type (SAD) and premenstrual dysphoric disorder (PMDD) are cyclical disorders characterized by so-called atypical depressive symptoms. In the present study we compared the point prevalence rates of PMDD between a sample of premenopausal female patients suffering from SAD and healthy female controls. METHODS: Forty-six female patients with SAD and 46 healthy controls were included in our study. All subjects underwent a semistructured clinical interview according to DSM IV criteria and completed the Seasonal Pattern Assessment Questionnaire. PMDD was diagnosed in a self-rating interview for PMDD according to DSM IV criteria. To verify the diagnosis of PMDD, all patients were followed up in stable summer remission using daily self-rating scales for two full menstrual cycles. RESULTS: Patients with SAD fulfilled significantly more often the diagnostic criteria for PMDD than female healthy controls (46% vs. 2%, respectively; chi-square: P<0.001). CONCLUSIONS: These results provide preliminary evidence for a high point prevalence rate of PMDD in premenopausal females with SAD. CLINICAL IMPLICATIONS: It would be worthwhile to investigate whether an additional diagnosis of PMDD has an impact on the clinical outcome and the response to bright light therapy in female patients with SAD.
Adult↗
Serotonin 5-HT1A receptor binding potential declines with age as measured by [11C]WAY-100635 and PET.
Positron emission tomography (PET) and [11C]WAY-100635 were used to examine the effect of age on serotonin-1A (5-HT1A) receptor binding potential (BP) in 19 healthy subjects. Regions of interest (ROI) were drawn on the co-registered magnetic resonance imaging (MRI) in orbitofrontal (OFC), dorsolateral prefrontal (DLPFC), anterior cingulate (ACC), lateral (LTC), and mediotemporal (MTC), parietal, occipital and cerebellar cortex, and the raphe nuclei. BP values were calculated using a simplified reference tissue method. In addition, a voxelwise analysis was performed using SPM99. Voxelwise analysis revealed a significant global decrease of 5-HT(1A) BP with age (set level <.001). ROI analysis revealed significant age-related 5-HT(1A) BP decreases in DLPFC (r = -0.56), ACC (r = -0.44), OFC (r = -0.42), LTC (r = -0.40), parietal (r = -0.65), and occipital cortex (r = -0.43), but not in MTC or raphe nuclei. Overall, cortical 5-HT(1A) BP declined by approximately 10% per decade, except for the MTC, where we did not find a significant age effect. Hence, careful age matching may be recommended for future studies using PET and [11C]WAY-100635 to examine 5-HT1A receptors.
Adult↗
Reboxetine in seasonal affective disorder: an open trial.
Seasonal affective disorder (SAD), winter type, is a condition characterized by the annual recurrence of depressive episodes during fall/winter, alternating with spring/summer euthymia or hypomania. Various neurotransmitters have been implicated in the etiology of SAD, the strongest evidence involving serotonin. Recently, increasing attention has been paid to the potential role of catecholaminergic pathways in the pathophysiology of SAD. We investigated the efficacy and tolerability of reboxetine, a selective noradrenaline inhibitor, in patients with SAD. Eleven out of sixteen patients who were included in a 6-week drug surveillance during winter season experienced full remission of depressive symptoms. Nine patients reported a rapid relief of preexistent severe atypical depressive symptoms within the first treatment week. Reboxetine might therefore be an effective and well-tolerated treatment option for SAD patients. In conclusion, our preliminary results are in line with evidence from recent studies suggesting that catecholaminergic systems might also be involved in the pathophysiology of SAD.
Adult↗
No change in striatal dopamine re-uptake site density in psychotropic drug naive and in currently treated Tourette's disorder patients: a [(123)I]-beta-CIT SPECt-study.
BACKGROUND: There is evidence that Tourette's disorder (TD) is associated with abnormalities in the dopaminergic system involving the dopamine transporter (DAT). Data from [(123)I]-beta-CIT single photon emission computed tomography (SPECT) studies and postmortem findings concerning DAT densities in TD patients are not conclusive. The objective of our study was to measure DAT densities with [(123)I]-beta-CIT binding in TD patients who were either psychotropic drug naive or currently treated with antipsychotics (AP) and healthy controls. METHOD: Altogether 20 TD patients were investigated. A total of 15 patients were psychotropic drug naive and five were currently treated with AP. Ten psychotropic drug naive patients were compared with ten age and sex matched healthy subjects. Five currently treated patients were compared with five age and sex matched psychotropic drug naive TD patients. The investigation was carried out using [(123)I]-beta-CIT (2-beta-carbomethoxy-3-beta(4-iodophenyl)-tropane and SPECT. Regions of interest (ROI) were drawn over the striatum and the cerebellum. RESULTS: The DAT densities measured by the striatal/cerebellar (S/C) binding ratio did not differ between drug naive TD patients and the controls. The difference between currently AP treated and psychotropic drug naive TD patients did not reach the level of significance. There was no correlation between the ratio and severity of tics and illness. CONCLUSION: Our study with psychotropic drug naive TD patients contributed to clarify the inconsistent results concerning the DAT.
Adult↗
Different fatal toxicity of neuroleptics identified by autopsy.
Autopsies and toxicological analyses at the Institute of Forensic Medicine revealed 85 fatal intoxications with neuroleptics in Vienna from 1991 to 1997. A total of 17 cases were linked to a single neuroleptic (NL) alone, while 68 deaths were attributed to a combination of NLs with other drugs. The most frequently detected agent was prothipendyl (n=41). During the study period the number of defined daily doses of high-potency NLs prescribed increased significantly (P< or =0.001) due to increased prescribing of new atypical antipsychotics. The quantity of intermediate- and low-potency NLs dispensed remained stable. The most frequently prescribed NL was haloperidol. The relative toxicities of different NLs were calculated by dividing the number of deaths caused by this NL into the number of defined daily doses prescribed in the observation period (f-value). Single-substance intoxications and multiple-substance intoxications were distinguished. The highest f-values were associated with low-potency NLs, especially with prothipendyl, chlorprothixene and levomepromazine. Low f-values were found for the group of high-potency NLs, including flupentixol, fluphenazine, haloperidol and pimozide, as well as olanzapine. Compared to the f-values for all NLs prescribed, f-values for low-potency NLs were shown to be significantly higher concerning single-substance intoxications (P< or = 0.05) and multiple-substance intoxications (P < or = 0.001), while f-values for high-potency NLs were significantly lower (P< or = 0.05 and P< or = 0.001). We are not aware of the psychiatric diagnoses in our post-mortem sample. However, the present results indicate that careless use of low-potent NLs should be avoided in patients with a potential risk of accidental or suicidal overdose.
Adult↗
Panic disorder: the place of benzodiazepines and selective serotonin reuptake inhibitors.
This article reviews the efficacy of the benzodiazepines and the selective serotonin reuptake inhibitor class of antidepressant in the treatment of panic disorder. The benzodiazepine alprazolam has been used successfully in the treatment of panic disorder, but its long-term use presents problems with dependence. Since panic may be mediated by a dysfunction of serotonin neuronal pathways, there is a rationale for treatment with antidepressants that modulate serotonergic systems. In clinical trials, members of the SSRI class of antidepressant reduced panic attack frequency to zero in 36-86% of patients and were well tolerated over long-term administration, all important factors in ensuring patient compliance. In addition, antidepressants are preferable to benzodiazepines in the treatment of panic and comorbid depression, of which there is a high prevalence among panic disorder patients. This review emphasises the need for long-term treatment of this chronic and disabling condition with a therapy that is well tolerated and provides complete and sustained recovery from panic attacks, and resolution of anticipatory anxiety.
Animals↗