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Biomedical subjects

Siegfried Kasper

Publications and source records attributed to Siegfried Kasper.

At least 73 records · Page 4Linked to original sources

[Electroconvulsive therapy as maintenance therapy and for prevention of recurrence in psychiatric disorders and Parkinson disease].

Electroconvulsive therapy is a reliable and safe option for patients with psychiatric disorders who are resistant or intolerant to medication as these patients usually respond quickly to this form of treatment. For clinicians, the management of these often severely ill patients is an important challenge given the high rate of relapse of these disorders. Maintenance electroconvulsive therapy is an interesting treatment option for these patients. Until now, only few controlled studies exist about the long-term outcome of this treatment in depressive disorders and other psychiatric disorders. Altogether, this form of outpatient prophylactic therapy has been found to be safe, well tolerated, and efficacious in relapse prevention. Moreover, it has been found to reduce hospitalization rates. Particularly in the elderly, and in patients who have been shown to be refractory to medication regimens, maintenance electroconvulsive therapy should be seriously considered as a means to reduce the risk of recurrence of illness. In Parkinson's disease maintenance electroconvulsive therapy is not widely established although its usefulness has been documented in numerous studies. First-line evidence data on incidence, dimensions and outcome of cognitive side effects under maintenance electroconvulsive therapy is still warranted.

Electroconvulsive Therapy↗

Effects of tryptophan depletion and catecholamine depletion on immune parameters in patients with seasonal affective disorder in remission with light therapy.

BACKGROUND: Altered immunologic parameters are found in symptomatic depressed patients relative to remitted depressed patients and healthy controls. We investigated whether tryptophan depletion and catecholamine depletion induce alterations in immunologic parameters in patients with seasonal affective disorder remitted on light therapy, and whether these changes are associated with changes in mood. METHODS: Remitted patients with seasonal affective disorder underwent tryptophan depletion, catecholamine depletion, and sham depletion in a prospective randomized, double-blind crossover design. Measures of depression, plasma levels of tryptophan and catecholamine metabolites, and plasma levels of cytokines (sIL-4, IL-6, neopterin, sTNF-R1 and sTNF-R2) were obtained at baseline, and 7, 24, and 30 hours after monoamine depletion. RESULTS: Tryptophan depletion decreased plasma total and free tryptophan levels; catecholamine depletion decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels. Tryptophan depletion and catecholamine depletion, but not sham depletion, induced a transient exacerbation of depressive symptoms (p <.001); plasma neopterin levels increased during tryptophan depletion and catecholamine depletion (p <.05). Tryptophan depletion and catecholamine depletion induced a transient reduction of plasma sIL-4 levels (p <.05). A significant correlation was found between sIL-4R levels and depression ratings after tryptophan depletion (r = -.61, p <.05). CONCLUSIONS: The monoamine depletion-induced alterations of humoral and cellular immunity suggest a potential role of immunologic parameters in the pathophysiology of seasonal affective disorder; however, the results must be considered preliminary and require further study.

Adult↗

Placebo-controlled studies in depression: necessary, ethical and feasible.

Placebo-controlled trials are used widely in the development of new pharmacological treatments. They have sometimes been challenged as being unethical, in clinical situations where patients can receive an existing effective and acceptable treatment. It has been argued that studies of potential antidepressants should employ only a comparator-controlled design, whereby new compounds have to be found at least as efficacious as existing treatments. By contrast, others have argued that sole use of comparator-controlled trials is itself unethical, as more patients will be exposed to potentially unhelpful treatments. This article reviews the rationale for conducting placebo-controlled treatment studies in depressed patients, examines the underlying ethical issues, and describes the provisions that should be applied when investigating the efficacy and tolerability of potentially valuable new antidepressant treatments. Placebo-controlled studies of new antidepressants are justified, both scientifically and ethically; restrictions on placebo-controlled investigations will hinder the arrival of more efficacious and better tolerated antidepressants.

Antidepressive Agents↗

Milnacipran in the treatment of bulimia nervosa: a report of 16 cases.

Controlled trials in patients with bulimia nervosa have demonstrated efficacy of antidepressant medications with serotonergic function (e.g. fluoxetine) as well as noradrenergic function (e.g. desipramine). Sixteen out-patients with bulimia nervosa according to DSM-IV criteria were treated in a drug surveillance with 100 mg of milnacipran, a specific serotonin and noradrenaline reuptake inhibitor (SNRI). Ten patients completed the 8-week observation period. The reasons for premature attrition were improvement in one patient (no. 12), a generalized exanthema in one patient (no. 7), severe nausea in one patient (no. 8) and non-compliance due to non-drug-related reasons in three patients (no. 1, 2, and 16). An intent-to-treat analysis exhibited a significant reduction in weekly binge eating and vomiting frequency from baseline to the end of treatment. Three patients stopped binge eating and purging completely during the last week of treatment. Furthermore, there was a concomitant decrease of depression ratings (HAMD, BDI). Our preliminary data give rise to the notion that milnacipran may be promising in the treatment of bulimia nervosa.

Adult↗

Clonazepam in the long-term treatment of patients with unipolar depression, bipolar and schizoaffective disorder.

The value of a long-term treatment with clonazepam in the prophylaxis of affective disorder is discussed controversially in the scientific literature. Altogether there are only a few reports on the use of this compound as a mood stabilizer, most of them describing patients suffering from bipolar affective disorder. The aim of this investigation was to evaluate clonazepam as a phase prophylactic medication in affective disorder. We conducted a retrospective chart review in 34 out-patients of our lithium clinic (15 suffering from unipolar depression, 15 from bipolar disorder, four from schizoaffective disorder), who had been treated with clonazepam as a long-term medication. Clonazepam was either given as monotherapy, or as in the case of lithium non-responders, as adjunctive therapy. Patients with unipolar depression had significantly (P=0.026) less depressive episodes after initiation of treatment with clonazepam. Patients with bipolar disorder did not benefit from this therapy. Neither manic/hypomanic phases nor depressive episodes were reduced in this group of patients. Interestingly, clonazepam also reduced affective phases in our four schizoaffective patients on a trend level. Our results indicate that patients with unipolar depression may benefit from a maintenance treatment with clonazepam. Due to methodological limitations our results need to be replicated in controlled double-blind randomized clinical trials.

Adult↗

Issues in the treatment of bipolar disorder.

Bipolar disorder is a chronic, recurring illness that requires long-term prophylactic treatment. However, treatment is often complicated by misdiagnosis and inappropriate medication selection. A number of therapies are available for the treatment of bipolar disorder and the ultimate therapeutic choice depends on the individual patient's current symptoms, disease history, and comorbid illnesses. However, research is needed to improve the overall prognosis for patients with bipolar depression, particularly because approximately 20% of patients commit suicide. Mania is the most dramatic expression of bipolar disorder and may overshadow the impact of the depressive phase of the illness. Compared with mania, episodes of bipolar depression are more frequent, of longer duration, and are associated with higher rates of morbidity and mortality. Therefore, successful treatment and prevention of bipolar depression remains an essential treatment goal.

Antidepressive Agents↗

Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia.

Aripiprazole is a novel atypical antipsychotic for the treatment of schizophrenia. It is a D2 receptor partial agonist with partial agonist activity at 5-HT1A receptors and antagonist activity at 5-HT2A receptors. The long-term efficacy and safety of aripiprazole (30 mg/d) relative to haloperidol (10 mg/d) were investigated in two 52-wk, randomized, double-blind, multicentre studies (using similar protocols which were prospectively identified to be pooled for analysis) in 1294 patients in acute relapse with a diagnosis of chronic schizophrenia and who had previously responded to antipsychotic medications. Aripiprazole demonstrated long-term efficacy that was comparable or superior to haloperidol across all symptoms measures, including significantly greater improvements for PANSS negative subscale scores and MADRS total score (p<0.05). The time to discontinuation for any reason was significantly greater with aripiprazole than with haloperidol (p=0.0001). Time to discontinuation due to adverse events or lack of efficacy was significantly greater with aripiprazole than with haloperidol (p=0.0001). Aripiprazole was associated with significantly lower scores on all extrapyramidal symptoms assessments than haloperidol (p<0.001). In summary, aripiprazole demonstrated efficacy equivalent or superior to haloperidol with associated benefits for safety and tolerability. Aripiprazole represents a promising new option for the long-term treatment of schizophrenia.

Acute Disease↗

Quantification of metabolic differences in the frontal brain of depressive patients and controls obtained by 1H-MRS at 3 Tesla.

RATIONALE AND OBJECTIVES: This study compared metabolic differences in the frontal brain of depressed patients versus age- and sex-matched controls using proton magnetic resonance spectroscopy and absolute quantification of metabolites (NAA, Cr, Cho, mI) at 3 Tesla. METHODS: Short-echo-time stimulated echo acquisition mode (TE/TM/TR=20/30/6000 milliseconds) was applied in the prefrontal region of 17 depressed patients and 17 age- and sex-matched controls. Metabolic ratios, ie, N-acetyl-aspartate/creatine (Cr), choline/Cr, and myo-inositol/Cr, and absolute concentrations (using internal water as a reference together with LCModel-based spectra fitting) were calculated and compared between groups and published reference data. RESULTS: Metabolic ratios showed significantly lower N-acetyl-aspartate/Cr (P = 0.016/0.006, left/right), choline/Cr (P = n.s./0.016), and myo-inositol/Cr (P = 0.022/0.026) for depressive patients versus controls. However, depressive patients showed significantly higher absolute concentrations of Cr (P = 0.017/0.0004) compared with controls with no differences in all other metabolites estimated. CONCLUSIONS: The authors demonstrate that absolute quantification of metabolite concentration is essential in properly identifying pathologic differences of brain metabolites in depression.

Adult↗

Relationship between power spectra of the awake EEG and psychomotor activity patterns measured by short-term actigraphy.

Actigraphy is a quantitative method for the measurement of motor activity. In the present study, actigraphy was used to examine psychomotor correlates of brain activity. Thirty-four psychiatric patients (17 males and 17 females) with different diagnoses participated in this investigation. Directly after EEG recording, motor activity was measured with a wrist actimeter for 15 min in patients in the sitting position. The EEG was quantified by spectrum analysis, and the power spectra as well as other EEG-derived variables were correlated with actigraphic parameters. Occipital and temporoparietal beta1 power was statistically significantly higher in patients with higher activity scores and lower in those with a high density of sleep (SB) or wake bouts (WB). A high density of SB or WB was also positively correlated with higher mean alpha power. Immobile phases measured by actigraphy were positively associated with occipital alpha and with frontal/frontopolar delta activity, preferentially on the side of the left hemisphere. Our results, while preliminary, suggest that short-term actigraphy may be apt to reflect central nervous system arousal.

Benzodiazepines↗

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders, Part II: Treatment of Mania.

Identical to the preceding guidelines of this series, these practice guidelines for the biological, mainly pharmacological treatment of acute bipolar mania were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of acute mania. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, from recent proceedings of key conferences, and from various national and international treatment guidelines. Their scientific rigor was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was finally not only graded, but has also been commented by the experts of the task force to ensure practicability. Key words: bipolar disorder, mania, acute treatment, evidence-based guidelines, pharmacotherapy, antipsychotics, mood stabiliser, electroconvulsive therapy.

Algorithms↗

Quetiapine in the treatment of borderline personality disorder.

Affective dysregulation, impulsivity and cognitive-perceptual difficulties are the psychopathological nuclear dimensions of Borderline Personality Disorder (BPD). Psychopharmacological treatment may become necessary during episodes of acute decompensation in which suicidal or self-destructive behaviour erupts. Some classes of psychotropic drugs have demonstrated efficacy in diminishing symptom severity and optimising functioning, such as antidepressants, mood stabilizers, benzodiazepines, opiate antagonists and antipsychotics. Conventional antipsychotics are the best-studied psychotropic medications for BPD, but nonadherence is often due to their severe side effects. Preliminary data reveal efficacy of atypical antipsychotics in BPD. We describe the impact of the novel antipsychotic drug quetiapine on severe self-mutilation in two female patients with the diagnoses of BPD. In both cases, monotherapeutic treatment with quetiapine was well tolerated and resulted in a marked improvement of impulsive behaviour and, over time, overall level of function. Though promising, our findings have to be regarded as preliminary. Due to the overall paucity of data there still is insufficient evidence to make a strong recommendation concerning continuation and maintenance therapy with atypical antipsychotics in BPD. Thus, there is a clear need for further controlled studies to evaluate pharmacological treatment options for this disorder.

Adult↗

Circadian clock-related polymorphisms in seasonal affective disorder and their relevance to diurnal preference.

Disturbed circadian rhythms have been observed in seasonal affective disorder (SAD). The aim of this study was to further investigate this connection, and to test for potential association between polymorphisms in circadian clock-related genes and SAD, seasonality (seasonal variations in mood and behavior), or diurnal preference (morningness-eveningness tendencies). A total of 159 European SAD patients and 159 matched controls were included in the genetic analysis, and subsets were screened for seasonality (n=177) and diurnal preference (n=92). We found that diurnal preference was associated with both SAD and seasonality, supporting the hypothesis of a link between circadian rhythms and seasonal depression. The complete case-control material was genotyped for polymorphisms in the CLOCK, Period2, Period3, and NPAS2 genes. A significant difference between patients and controls was found for NPAS2 471 Leu/Ser (chi(2)=9.90, Bonferroni corrected P=0.035), indicating a recessive effect of the leucine allele on disease susceptibility (chi(2)=6.61, Bonferroni corrected P=0.050). Period3 647 Val/Gly was associated with self-reported morningness-eveningness scores (n=92, one-way ANOVA: F=4.99, Bonferroni corrected P=0.044), with higher scores found in individuals with at least one glycine allele (t=3.1, Bonferroni corrected P=0.013). A second, population-based sample of individuals selected for high (n=127) or low (n=98) degrees of seasonality, was also genotyped for NPAS2 471 Leu/Ser. There was no significant difference between these seasonality extreme groups, and none of the polymorphisms studied were associated with seasonality in the SAD case-control material (n=177). In conclusion, our results suggest involvement of circadian clock-related polymorphisms both in susceptibility to SAD and diurnal preference.

Analysis of Variance↗

St John's wort extract (LI 160) in somatoform disorders: results of a placebo-controlled trial.

RATIONALE AND OBJECTIVE: Preliminary data have shown that St John's wort might possess some specific efficacy in patients with somatoform complaints. Therefore, the efficacy of the Hypericum extract LI 160 in patients with somatoform disorders should be studied in a double-blind placebo-controlled fashion. METHODS: This was a multicentre, randomised, placebo controlled, 6-week trial comparing the efficacy of LI 160 (600 mg/day) and placebo in 151 out-patients suffering from somatization disorder (ICD-10: F45.0), undifferentiated somatoform disorder (F45.1), or somatoform autonomic dysfunctions (F45.3). The primary outcome measure was the decrease of the Hamilton Anxiety Scale, subfactor somatic anxiety (HAMA-SOM), during the trial period. RESULTS: LI 160 was superior effective concerning the primary outcome criterion HAMA-SOM [decrease from 15.39 (SD 2.68) to 6.64 (4.32) in the Hypericum group and from 15.55 (2.94) to 11.97 (5.58) in the placebo group (statistically significant difference, P=0.001)]. This was corroborated by the result of a statistically significant superior efficacy in the outcome criteria additionally used such as Clinical Global Impression, HAMA-total score, HAMA, subscore psychic anxiety, Hamilton Depression Scale, Self-Report Symptom Inventory 90 items - revised (SCL-90-R), and SCL-90-R, subscore somatic anxiety. The efficacy of LI 160 was preserved after splitting the population in those with and those without mild depressive symptoms [corrected]. Tolerability of LI 160 was excellent. CONCLUSION: The data from this trial show excellent efficacy and tolerability for LI 160 in somatoform disorders. The efficacy is independent of an existing depressive mood. This is the first study showing the efficacy of a drug in patients with somatisation disorder independent of depressive symptomatology.

Adolescent↗

Genome scan for susceptibility loci for schizophrenia and bipolar disorder.

BACKGROUND: Despite the widely accepted view that schizophrenia and bipolar disorder represent independent illnesses and modes of inheritance, some data in the literature suggest that the diseases may share some genetic susceptibility. The objective of our analyses was to search for vulnerability loci for the two disorders. METHODS: A genomewide map of 388 microsatellite DNA markers was genotyped in five schizophrenia and three bipolar disorder Austrian families. Linkage analyses was used to compute the usual parametric logarithm of the likelihood of linkage (LOD) scores and nonparametric linkage analysis (NPL scores Z(all)) was used to assess the pattern of allele sharing at each marker locus relative to the presence of the disease (GENEHUNTER). Affected status was defined as severe affective disorder or schizophrenia. RESULTS: Across the genome, p values associated with NPL scores resulted in evidence (i.e., p <.0007) for linkage at marker D3S1265 on chromosome 3q (NPL score Z (all) = 3.74, p =.0003). Two other markers (on 3q and 6q) showed p values of <.01. CONCLUSIONS: We detected a potential susceptibility locus for bipolar disorder and schizophrenia on chromosome 3q, which has not been reported previously. The possibility of a false positive result has to be taken into account. Our data suggest shared loci for schizophrenia and bipolar affective disorders and are consistent with the continuum model of psychosis.

Austria↗

Striatal dopamine-2 receptor occupancy as measured with [123I]iodobenzamide and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol.

RATIONALE: Extrapyramidal symptoms (EPS) are common with conventional antipsychotics. Clozapine and other novel antipsychotic substances with lower in vitro affinity for dopamine-2 (D(2)) receptors have a lower propensity to induce EPS. OBJECTIVE: We investigated whether striatal D(2) receptor occupancy predicted the occurrence of EPS with atypical antipsychotics and the typical neuroleptic haloperidol. METHODS: [(123)I]Iodobenzamide (IBZM) and single photon emission tomography (SPECT) were used to quantify receptor occupancy in 71 patients treated with antipsychotics. EPS were rated according to the Simpson-Angus scale (SAS). EPS were deemed clinically relevant, if the SAS score was > or = 5 and/or anticholinergic medication was required. Patients received atypical antipsychotic monotherapy for at least 14 days with amisulpride ( n=2), clozapine ( n=6), haloperidol ( n=10), olanzapine ( n=6), quetiapine ( n=4), risperidone ( n=14), sertindole ( n=13), or zotepine ( n=16). RESULTS: The striatal D(2) receptor occupancy ranged from < 20% to almost saturation. The lowest occupancy was seen with quetiapine and clozapine, the highest with haloperidol. Twenty-two of 71 patients (29%) experienced clinically relevant EPS. These patients displayed significantly higher mean striatal D(2) receptor occupancy (77%) than those without EPS (61%; P=0.002). We found a positive correlation between the percentage of striatal D(2) receptor occupancy and the SAS score ( r=0.28; P=0.02), despite 18 of these patients receiving anticholinergics, thus lowering their SAS score. CONCLUSIONS: Striatal D(2) receptor occupancy as measured with [(123)I]IBZM and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol. In vivo imaging of brain receptors with SPECT may provide a useful clinical tool to titrate doses individually and avoid motor side effects in patients treated with novel antipsychotics.

Adolescent↗