Quetiapine in a delusional depressed elderly patient: no EPS and a favourable outcome.
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Aged↗
Biomedical subjects
S Kasper
Publications and source records attributed to S Kasper.
In BCR-ABL-positive cells, STAT-5 tyrosine-phosphorylation integrates signals induced by imatinib mesylate and Ara-C.
In BCR-ABL-positive cells, the transcription factor STAT-5 is constitutively activated by tyrosine phosphorylation. STAT-5 activation results in upregulation of bcl-X(L) and increased resistance to induction of apoptosis. Here, we investigated the effects of imatinib mesylate and cytosine arabinoside (Ara-C) on STAT-5 tyrosine-phosphorylation, cellular proliferation and induction of apoptosis in cell lines and primary hematopoietic cells. Imatinib mesylate treatment strongly suppressed STAT-5 tyrosine-phosphorylation in K562 and primary CML blasts. In contrast to JAK-2 and PI-3-kinase inhibition, exposure of K562 cells to imatinib mesylate resulted in obvious suppression of proliferation. Reduced cell growth was due to specific induction of caspase activation followed by apoptotic cell death. In addition, we investigated the effects of Ara-C on STAT-5 tyrosine-phosphorylation. Exposure to Ara-C resulted in significant downregulation of STAT-5 tyrosine-phosphorylation and inhibition of DNA binding. Treatment of K562 cells with Ara-C in combination with imatinib mesylate revealed synergistic effects at the level of STAT-5 tyrosine-phosphorylation and DNA binding, Hck tyrosine-phosphorylation, cell growth and induction of apoptosis. Overall, in this report we demonstrate that STAT-5 tyrosine-phosphorylation is a specific target of imatinib mesylate and Ara-C. Our results suggest that, in combination therapy, inhibition of STAT-5 tyrosine-phosphorylation may be responsible for synergistic or additive effects on BCR-ABL-positive cells.
Antineoplastic Agents↗
A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder.
Serotonergic mechanisms are thought to play an important role in the pathogenesis of seasonal affective disorder (SAD). The expression of the serotonin transporter (5-HTT) is regulated in part by an insertion/deletion polymorphism in the serotonin transporter gene promoter region (5-HTTLPR). The 5-HTTLPR short allele (s) has been associated with anxiety-related personality traits and depression, and one study observed an association between the 5-HTTLPR s-allele and SAD and the trait of seasonality. We genotyped 138 SAD patients and 146 healthy volunteers with low seasonality for 5-HTTLPR. No difference between patients and controls was found for genotype distribution and s-allele frequency. However, genotype distribution and allele frequencies were strongly associated with DSM-IV depression subtypes. Melancholic depression was associated with the 5-HTTLPR long (l) allele and atypical depression with the 5-HTTLPR s-allele (two-sided Fisher's exact test: genotype distribution: P=0.0038; allele frequencies: P=0.007). Our data are compatible with the hypothesis of a disease process that is not causally related to 5-HTTLPR, but involves 5-HT neurotransmission and 5-HTTLPR somewhere on its way to phenotypic disease expression.
Bipolar Disorder↗
Cluster analysis of symptoms during antidepressant treatment with Hypericum extract in mildly to moderately depressed out-patients. A meta-analysis of data from three randomized, placebo-controlled trials.
RATIONALE: Although extracts from Hypericum have long played a major role in the treatment of mild to moderate depression, information pertaining to the drug's therapeutic profile is sparse. OBJECTIVES: To investigate whether the administration of the Hypericum extract has a selective effect on particular signs and symptoms of depression as opposed to a more general acceleration of recovery. METHODS: A meta-analysis was performed on the original data of three double-blind, randomized multicenter trials, during which 544 out-patients suffering from mild to moderate depression according to DSM-IV criteria received 3x300 mg/day Hypericum extract (WS 5570 or WS 5572) or placebo over a double-blind treatment period of 6 weeks. The primary outcome measure for treatment efficacy in the original trials was the change in the total score of the Hamilton Rating Scale for Depression (HAMD, 17-item version) between baseline and treatment end. The relationship between the symptoms of depression represented by the items of the HAMD was assessed by means of cluster analysis and individual item analysis. RESULTS: Two clusters of items were identified which were stable in several independent subsets of the full data set. While cluster 1 (HAMD items 1, 2, 3, 7, 8, 12, 13, 14, 16) was interpreted to represent the core symptoms of depression (including somatic aspects), cluster 2 (items 4, 5, 6, 9, 10, 11, 15, 17) was primarily composed of items assessing depression-related anxiety and insomnia. In both clusters, Hypericum extract reduced the symptoms of depression more effectively than placebo. However, the herbal drug was particularly effective in the core symptoms of the disorder. CONCLUSIONS: The results indicate that Hypericum extract accelerated the recovery from depression in a rather general manner, by influencing all investigated signs and symptoms of the disease. The drug's therapeutic profile was thus found to be similar to the profile of selective serotonin reuptake inhibitors.
Antidepressive Agents↗
[Fatal poisonings with antidepressive drugs and neuroleptics. Analysis of a correlation with prescriptions in Vienna 1991 to 1997].
As a result of the increasing use of selective serotonin reuptake inhibitors (SSRI), the number of antidepressants (AD) prescribed in Vienna doubled from 1991 to 1997. In the same period, autopsies and chemical analyses performed at the Institute of Forensic Medicine, University of Vienna, revealed a total of 164 fatal intoxications by means of AD. In this study, the number of fatal intoxications per million defined daily doses prescribed was determined and referred to as the fatal toxicity index (f-index). For both single- and multiple-substance intoxications, it proved to be significantly (p < 0.001) lower with SSRI than with tricyclic antidepressants (TCA). Single-substance intoxications (n = 30) were seen exclusively in TCA. Concerning neuroleptics (NL), the increase in prescriptions observed in the study period (plus 30%) was less pronounced, and they were found to be involved in 85 fatal intoxications. Also in NL, those of the tricyclic type (TCNL) showed a significantly (p < 0.001) higher f-index than other groups. Out of a total of 17 single-substance intoxications, 14 were caused by TCNL and none by butyrophenones or haloperidol. The present study demonstrates that the prescription of TCA or TCNL involves a relatively high risk of fatal intoxication.
Antidepressive Agents↗
[Tourette's syndrome - a review].
Tourette's syndrome (TS) is a neuropsychiatric disorder characterised by the occurrence of chronic motor and vocal tics that usually begin in childhood. A prevalence of 4-5/10.000 individuals is estimated. Tourette's syndrome patients frequently show comorbidity with other psychiatric disorders such as obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), anxiety, and affective disorders. Some forms of OCD seem to share a common genetic etiology with TS and to be a facultative part of the TS phenotypic spectrum. Based on MRI, positron emission tomography (PET), and single photon emission computed tomography (SPECT), data alterations in the cortico-striato-pallido-thalamo-cortical functional systems have been discussed. Within these systems, dopaminergic neurotransmission is thought to play an important role in the pathophysiology of TS. Autoimmunological mechanisms seem to be important in some subtypes of TS and OCD that are triggered or exacerbated by infections with hemolytic streptococci. In these cases, immune modulatory therapy proved to be efficient. To date, there is no established treatment regimen for TS. The medications used most frequently are antipsychotics.
Antipsychotic Agents↗
[Seasonal affective depression in 2 German speaking university centers: Bonn, Vienna. Clinical and demographic characteristics].
Six hundred ten patients with seasonal affective disorder (SAD) were diagnosed and treated at the university hospitals for psychiatry in Bonn, Germany (1989-1992) and Vienna, Austria (1993-2001). The aim of this study was to compare our sample with other SAD populations in the literature and to investigate differences between the two study locations. We found female:male sex ratios of 5.0:1.0 in unipolar depressives and 1.5:1.0 in patients with bipolar affective disorder. Of our patients, 21.7% suffered from bipolar II disorder, and 1.3% were diagnosed as having bipolar I. Our patients obtained a mean global seasonality score (GSS) of 15.4. Women had a higher GSS than men (t = 2.127, P = 0.035), and Viennese patients had higher scores than patients in Bonn (t = 3.104, P = 0.002). Totals of 66.3% of all patients suffered from atypical depression and 17.8% from melancholic depression. Patients with atypical depression were more frequent in Vienna, whereas patients with melancholic depression predominated in Bonn (chi 2 = 54.952, df = 2, P < 0.001). The demographic and clinical characteristics of the patients described in this article confirm the findings of other epidemiological investigations obtained in non-German-speaking samples.
Adult↗
Intravenous antidepressant treatment: focus on citalopram.
During the last decade, the number of patients who consult primary care physicians or psychiatrists for symptoms of depression has doubled. The majority of depressed patients are prescribed oral medication; however, in several European countries antidepressant therapy may be initiated with a daily intravenous infusion. The choice of intravenous antidepressants was previously limited to agents such as dibenzepine, doxepin, clomipramine and viloxazine. More recently, the selective serotonin reuptake inhibitor (SSRI) citalopram has been administered as an intravenous infusion to severely depressed patients. The results from both open and double-blind clinical studies with intravenous citalopram suggest that it is an effective and well-tolerated treatment for depression. Moreover, when treatment is initiated by infusion and continued orally, citalopram is at least as effective as clomipramine, doxepin and viloxazine. As with oral treatment, adverse events experienced by patients are mild to moderate in severity with 50 % of patients reporting no adverse events. The high bioavailability of citalopram indicates that the switch from intravenous to oral citalopram would prevent a deterioration of symptoms as plasma drug concentrations would be maintained. Thus citalopram, the only SSRI available as an intravenous formulation, may be a useful addition for the treatment of severely depressed patients who may benefit from more intensive therapy. The aim of this paper is to review available data detailing the clinical outcome of intravenously administered citalopram in depressed patients.
Administration, Oral↗
Changes of clinical pattern in seasonal affective disorder (SAD) over time in a German-speaking sample.
OBJECTIVE: The goals of this study are to provide estimates of clinical and demographic variables of patients with seasonal affective disorder (SAD) in Germany and Austria, to compare our results with those of previously published SAD studies, and to find out whether the clinical pattern of SAD remained stable over several years. METHOD: We investigated 610 SAD patients from the outpatient clinics in Bonn (n = 190) and Vienna (n = 420). Patients in Bonn were recruited in the fall-winter season of the years 1989-1992, those in Vienna in the years 1993-2001. RESULTS: We observed a change in the clinical pattern in our patients: patients from Bonn, who were diagnosed and treated about 5 years earlier, were more likely to suffer from melancholic depression, whereas Viennese patients rather suffered from atypical depression (chi(2) = 54.952, df = 2, p < 0.001). The symptoms of hypersomnia, daytime fatigue, increased eating and carbohydrate-craving were more frequent in the Viennese sample, anxiety and deterioration of patients' capacity to perform at work predominated in Bonn. In addition, patients from Vienna obtained a higher GSS (global seasonality score, measured by the SPAQ - Seasonal Pattern Assessment Questionnaire) than those from Bonn (15.7 +/- 3.3 and 14.6 +/- 4.1 respectively; t = 3.104, p = 0.002). Taken together, our results were in good accordance to other published SAD materials, but we were able to demonstrate that our patients reported "feeling worst" (measured by item 13H of the SPAQ) in November and December, whereas SAD patients in the USA clearly had their worst months in January and February. CONCLUSIONS: We suggest that an increase in awareness of fall-winter depression in the last decade by both doctors, who referred patients, as well as patients or the entire population must have caused patients to sign up for light therapy at the Viennese SAD clinic because of having heard about the atypical symptom profile. This increased awareness of SAD can also be measured by a statistically significant reduction in the diagnostic latency (from the age of onset to the diagnosis of SAD) when comparing the two study locations.
Adult↗
[Pharmacotherapy of seasonal depression].
Seasonal affective disorder (SAD), first described in 1984, is a condition characterized by recurring depressive episodes in fall and winter alternating with nondepressive episodes in spring and summer. Various neurotransmitters have been implicated in the etiology of SAD, with the strongest evidence for an involvement of serotonin. Moreover, researchers have focused on the development of treatment modalities for SAD. Despite the proven efficacy of light therapy in SAD, some patients do not experience sufficient relief of depressive symptoms with light, and a number of them feel unable to comply because of logistical difficulties in administering bright light therapy. Comparatively few studies have examined the role of pharmacotherapy in the treatment of SAD. So far, selective serotonin reuptake inhibitors and possibly compounds with a distinct noradrenergic mechanism of action seem to be the treatment of choice for seasonal depression. There is, however, a clear need for further placebo-controlled studies to evaluate pharmacological treatment options for SAD.
Antidepressive Agents↗
A meta-analysis of randomized controlled trials of tianeptine versus SSRI in the short-term treatment of depression.
A meta-analysis was performed to compare the efficacy of tianeptine and selective serotonin reuptake inhibitors (SSRI) in the short-term treatment of depression. Consecutive selection and inclusion processes allowed five studies to be selected: two studies on tianeptine versus fluoxetine, two studies on tianeptine versus paroxetine, and one study on tianeptine versus sertraline. A total of 1348 patients were included in the five studies; 681 subjects received an SSRI and 667 tianeptine. A strict step-by-step methodology was applied in order to legitimize this meta-analysis and to interpret the results. Considering all the patients or those with a Montgomery-Asberg Depression Rating Scale (MADRS) inclusion score greater than 28, none of the assessed parameters (MADRS total score and responder rate) revealed any significant difference between the two treatment groups. Further analysis based on clinical global impression (CGI) items found no significant difference, except for CGI item 3 (therapeutic index), where a tendency (P=0.06 or 0.07 depending on the methodology) was found in favor of tianeptine. All in all, this study confirmed that tianeptine is at least as effective as SSRI, with a trend for a better acceptability profile in the treatment of depressed patients.
Antidepressive Agents, Tricyclic↗
Intravenous mirtazapine in the treatment of depressed inpatients.
Mirtazapine is a novel antidepressant with a noradrenergic and specific serotonergic mode of action. So far, mirtazapine has been administered orally. This naturalistic study evaluates the antidepressant efficacy, safety, and tolerability of mirtazapine 15 mg/day administered intravenously to 27 inpatients with moderate to severe major depression. Compared with baseline, we found a significant decrease of the Hamilton Depressive Rating Scale (HDRS) total score (P<0.001). Side effects were mild and transient. Altogether, the results of this preliminary study show that intravenous mirtazapine is an effective, safe and well tolerated treatment for depressed inpatients.
Adrenergic alpha-Antagonists↗
Successful treatment of reboxetine-induced urinary hesitancy with tamsulosin.
Urinary hesitancy can be an uncomfortable side effect during antidepressant treatment. Clinicians often use the selective alpha(1A)-adrenoceptor antagonist, tamsulosin, to treat urinary hesitancy associated with prostate enlargement. We report here a series of case studies in which tamsulosin has been successfully used in the management of urinary hesitancy during therapy with the selective noradrenaline reuptake inhibitor reboxetine for major depressive disorder (MDD). Eight male adults (aged 43-64 years; DSM-IV diagnosis of MDD) who were receiving treatment with reboxetine (4-8 mg/day) were considered candidates for concomitant tamsulosin (0.4 mg/day) therapy. Tamsulosin was administered either as prophylaxis (n=4) or as treatment (n=4) for emergent urinary hesitancy. All patients experienced relief of urinary hesitancy within 20 min of tamsulosin therapy and this effect was sustained. Concomitant treatment with tamsulosin should be considered for those patients in whom urinary hesitancy may lead to withdrawal from reboxetine therapy.
Adrenergic alpha-Antagonists↗
The role of noradrenaline and selective noradrenaline reuptake inhibition in depression.
Depression is a common disorder that impacts on all aspects of a person's life. For the past 10 years, clinicians have focused on serotonin in their treatment of depression. This is largely due to the growing acceptance of the efficacy and safety of the selective serotonin reuptake inhibitors (SSRIs) in comparison with older tricyclic antidepressants (TCAs). However, evidence for a role of noradrenaline in depression has been accumulating for some time, beginning with the discovery that drugs which either caused or alleviated depression acted to alter noradrenaline metabolism. Until recently, the role of noradrenaline in depression was predicted from clinical experience with noradrenergic TCAs (desipramine, nortriptyline and protriptyline) and selective serotonin and noradrenaline reuptake inhibitors (venlafaxine, milnacipran). The licensing of reboxetine, a selective noradrenaline reuptake inhibitor now allows the role of noradrenaline in depression to be investigated directly. This review presents key data from the literature that support a role for noradrenaline in depression taking into account neurophysiology, psychopharmacology and clinical trial data.
Adrenergic Uptake Inhibitors↗
2-COM: an instrument to facilitate patient-professional communication in routine clinical practice.
OBJECTIVE: A simple patient-completed self-report instrument may facilitate patient-professional carer communication. METHOD: A 19-item self-report needs schedule was used in a sample of 243 out-patients with non-affective psychosis. Patients and professional carers commented on the usefulness of the instrument. In a subgroup of 95 patient-carer dyads, the professional carer was asked to rate the needs in addition to the patient. RESULTS: Patients scored their needs reliably and lower than the professionals (OR = 0.9, 95% CI: 0.9, 0.97). Concordance between patients and professional carers on individual needs was very low. More than 50% of the professional carers and more than 80% of the patients found 2-COM useful. The higher the number of needs indicated by the patient, the greater the discrepancy between patients and professional carers with regard to the usefulness of the schedule. CONCLUSION: 2-COM is a useful instrument to expose, and subsequently bridge, patient-professional carer discordance on patient needs.
Adult↗
Successful treatment of recurrent brief depression with reboxetine -- a single case analysis.
Recurrent Brief Depression (RBD) is a prevalent condition among the depressive illnesses, and is characterized by depressive episodes of a few days' duration occurring almost every month that are unrelated to the menstruation cycle. So far, RBD has not been shown to respond to antidepressive treatment in controlled clinical trials with citalopram, fluoxetine, flupenthixol, paroxetine, or mianserin using a "classical" parallel group design. However, successful RBD treatment on about sixty patients has so far been reported in one open trial with fluoxetine and in several cases with lithium, mirtazapine, and tranylcypromine. Furthermore, successful treatment of RBD has been reported in a few patients with carbamazepine, nimodipine, and verapamil in controlled double-blind single-case analyses using a flexible cross-over design.
Adult↗
Managing reboxetine-associated urinary hesitancy in a patient with major depressive disorder: a case study.
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Adrenergic Uptake Inhibitors↗
[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↗