Bipolar Disorder: Kasper S

Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Moller HJ, Kasper S. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · World J Biol Psychiatry. · Pubmed #19347775 No free full text.

Abstract: These updated guidelines are based on a first edition that was published in 2003, and have been edited and updated with the available scientific evidence until end of 2008. Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of acute mania in adults. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, from the clinical trial database clinicaltrials.gov, from recent proceedings of key conferences, and from various national and international treatment guidelines. Their scientific rigor was categorised into six levels of evidence (A-F). As these guidelines are intended for clinical use, the scientific evidence was finally asigned different grades of recommendation to ensure practicability.

Grunze H, Kasper S, Goodwin G, Bowden C, Möller HJ, Anonymous00338. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · World J Biol Psychiatry. · Pubmed #15346536 No free full text.

Abstract: As with the two preceding guidelines of this series, these practice guidelines for the pharmacological maintenance treatment of bipolar disorder 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 relating to maintenance treatment. The data used for these guidelines were extracted from a MEDLINE and EMBASE search, from recent proceedings from key conferences and various national and international treatment guidelines. The scientific justification of support for particular treatments was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was not only graded, but also reviewed by the experts of the task force to ensure practicality.

Grunze H, Kasper S, Goodwin G, Bowden C, Baldwin D, Licht RW, Vieta E, Möller HJ, Anonymous00027. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · World J Biol Psychiatry. · Pubmed #12582971 No free full text.

Abstract: 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.

Grunze H, Kasper S, Goodwin G, Bowden C, Baldwin D, Licht R, Vieta E, Möller HJ, Anonymous00265. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · World J Biol Psychiatry. · Pubmed #12478876 No free full text.

Abstract: These practice guidelines for the biological, mainly pharmacological treatment of bipolar depression 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 bipolar depression. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, and from recent proceedings of key conferences and 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 not only graded, but also commented on by the experts of the task force to ensure practicability.

Oswald P, Souery D, Kasper S, Lecrubier Y, Montgomery S, Wyckaert S, Zohar J, Mendlewicz J. · Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Brussels, Belgium. · Eur Neuropsychopharmacol. · Pubmed #17513092 No free full text.

Abstract: Although awareness on bipolar disorder has increased during the last decade, this condition remains characterized by a disabling burden, in terms of morbidity and functional impairment. This paper aims to review some critical issues in the current knowledge on Bipolar disorder. Although large European epidemiological studies are lacking, Bipolar disorder is characterized by a set of severe features, including an early age of onset, a chronic outcome and an important suicidal risk. A majority of bipolar patients also experience a comorbid Axis I condition, including substance abuse, anxiety disorder and attention-deficit hyperactivity disorder. This situation presents a therapeutic challenge, since antidepressants or methylphenidate may be associated with the risk of inducing mania. Recently, a large number of studies have provided evidence for the efficacy of new compounds in the treatment of both mania and bipolar depression, but also in long-term relapse prevention. Recent research has also allowed for the redefinition of the concept of mood stabilizer and for improving existing guidelines on the clinical management of Bipolar disorder.

Grunze H, Adli M, Bauer M, Berger M, Bergmann A, Bräunig P, Bschor T, Falkai P, Gastpar M, Greil W, Kasper S, Krüger S, Laux G, Müller WE, Naber D, Walden J. · Psychiatrische Klinik LMU, München. · Fortschr Neurol Psychiatr. · Pubmed #17427043 No free full text.

Abstract: During recent years valproate has been established as a cornerstone for the drug-treatment of bipolar disorder. In Germany, valproate was licensed both for the treatment of acute mania and for maintenance treatment in summer 2005. At this occasion, this review summarises the scientific evidence and clinical experience of well-known experts with valproate-treatment. It was concluded that valproate will continue to be of high clinical significance despite the recent increase of treatment alternatives, both in monotherapy and combination treatment of acute mania, mixed states and maintenance treatment.

Attarbaschi T, Kasper S. · Klinische Abteilung für Allgemeine Psychiatrie, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090 Wien, Osterreich. · Nervenarzt. · Pubmed #16773369 No free full text.

Abstract: The diagnosis and treatment of bipolar mania are extremely challenging. Therapeutic intervention for mania has traditionally relied on the use of lithium or divalproex as a first-line treatment option. However, due to the limited therapeutic range of these agents, typical neuroleptics have often been used. Although these have demonstrated efficacy in mania, they are often associated with significant side effects, especially extrapyramidal symptoms. Thus, atypical antipsychotics are increasingly preferred in the treatment of bipolar mania. In this review, data from controlled studies for several of the atypical antipsychotics in the treatment of mania are surveyed and issues in the selection of an appropriate atypical agent are discussed.

Pjrek E, Winkler D, Kasper S. · Department of General Psychiatry at the Medical University of Vienna, Vienna, Austria. · CNS Spectr. · Pubmed #16041297 links to  free full text

Abstract: Seasonal affective disorder is a common variant of recurrent major depressive disorder or bipolar disorder. Treatment with bright artificial light has been found to be effective in this condition. However, for patients who do not respond to light therapy or those who lack compliance, conventional drug treatment with antidepressants also has been proposed. Substances with selective serotonergic or noradrenergic mechanisms should be preferred over older antidepressants. Although there are a number of open and controlled studies evaluating different compounds, these studies were often limited by relatively small sample sizes. Furthermore, there are no studies specifically addressing bipolar seasonal depression. This article will review the published literature on pharmacotherapy of seasonal affective disorder.

Hirschfeld RM, Kasper S. · Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch at Galveston, TX 77555-0188, USA. · Int J Neuropsychopharmacol. · Pubmed #15458610 No free full text.

Abstract: Bipolar disorder is a recurrent lifelong condition associated with significant morbidity and mortality. The main goals of treatment are the acute management of manic/depressive episodes and the prevention of recurrence. Mood stabilizers are the basis of most treatment regimens. Although lithium is the classical mood stabilizer, dissatisfaction with its efficacy and tolerability has led to increased use of other mood- stabilizing agents, including anticonvulsants. Newer anticonvulsants such as oxcarbazepine may offer improved tolerability and fewer drug-drug interactions compared to older drugs like carbamazepine. A search of the literature shows that data from controlled clinical studies support the efficacy of carbamazepine in treating acute mania and as maintenance therapy. In addition, a growing body of data for oxcarbazepine suggests that this newer agent may have a similar efficacy profile to carbamazepine, with improved tolerability. This review presents a balanced selection of the key studies on carbamazepine and oxcarbazepine in bipolar disorder.

Calabrese JR, Kasper S, Johnson G, Tajima O, Vieta E, Yatham LN, Young AH. · Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA. · J Clin Psychiatry. · Pubmed #15119923 No free full text.

This publication has no abstract.

Kasper S. · Department of General Psychiatry, University Hospital for Psychiatry, Währinger Gürtel 18-20, 1090 Vienna, Austria. · Eur Neuropsychopharmacol. · Pubmed #12957718 No free full text.

Abstract: 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.

Kasper S, Stamenkovic M, Letmaier M, Schreinzer D. · Department of General Psychiatry, University of Vienna, Vienna, Austria. · Int Clin Psychopharmacol. · Pubmed #12570066 No free full text.

Abstract: Bipolar disorder is ranked as the sixth most important worldwide cause of disability. Current treatment is based chiefly on lithium and/or anticonvulsants, of which sodium valproate is the most widely used. A significant minority of patients fail to respond fully to current treatments, particularly those with mixed mania and/or rapid cycling. Many patients are unable to tolerate the side-effects of current therapy in the long term, and adverse effects may contribute to the high rate of noncompliance observed in bipolar disorder. The shortcomings of current treatments are reflected in poor outcomes: two-thirds of patients with bipolar disorder require hospitalization on more than one occasion; employment and social functioning are significantly lower than in control groups; 93% of carers suffer at least moderate distress; and 25-50% of patients are believed to attempt suicide at least once. Bipolar disorder shares some features with schizophrenia, and several atypical antipsychotics have demonstrated efficacy in bipolar disorder. Quetiapine has a particularly favourable tolerability profile, with placebo-level extrapyramidal symptoms and prolactin levels across the entire dose range combined with a neutral effect on weight during long-term use, and may be a valuable treatment option in acute mania and bipolar disorder.

Frey R, Schreinzer D, Heiden A, Kasper S. · Klinische Abteilung für Allgemeine Psychiatrie, Universitätsklinik für Psychiatrie, Währinger Gürtel 18-20, A-1090 Wien. · Nervenarzt. · Pubmed #11572099 No free full text.

Abstract: 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.

Montgomery SA, Schatzberg AF, Guelfi JD, Kasper S, Nemeroff C, Swann A, Zajecka J. · Imperial College School of Medicine, London, UK. · J Affect Disord. · Pubmed #11121826 No free full text.

Abstract: The treatment of bipolar depression requires the resolution of depression and the establishment of mood stability. A basic problem is that the treatments used in treating bipolar depression were developed and proven effective for other disease states: antidepressants for unipolar depression, and mood stabilizers for mania. The panel addressed four unresolved questions regarding depression in relation to bipolar disorder: (1) the relative effectiveness of different antidepressant treatments; (2) the relative likelihood of mood destabilization with different antidepressant treatments; (3) the effectiveness and role of mood-stabilizing medicines as antidepressants; and (4) the optimal approach to mixed states. The selection of an antidepressant depends both on its relative lack of mania- or hypomania-provoking potential and on its effectiveness against bipolar depression. There is little definitive evidence distinguishing effectiveness of the major groups of antidepressive agents, so side-effect profiles and pharmacokinetics are major considerations. The underlying bipolar disorder should be treated with mood stabilizers started simultaneously with any antidepressive treatments. Lithium, divalproex sodium and carbamazepine have all been found to be helpful, to some extent, in treating bipolar depressive episodes as well as for long-term mood stabilization. There is little evidence for long-term benefits of antidepressive agents in bipolar disorder, and some evidence that they may destabilize the disorder. Therefore, in contrast to the long-term use of mood-stabilizers, antidepressant use is recommended on a temporary basis. The duration of antidepressant treatment is determined by past history in terms of liability for mood destabilization, and by the ability of the patient to tolerate gradual antidepressant discontinuation without return of depression. Mixed states, where symptoms of depression and mania coexist, are regarded as a predictor of relatively poor response to lithium, and divalproex has been found to be more effective. Carbamazepine may too be useful in mixed states. Most patients with mixed states in actual practice require combinations of mood stabilizers, though there is little controlled data regarding such co-prescription, especially from a long-term perspective.

Attarbaschi T, Sacher J, Geiss-Granadia T, Klein N, Mossaheb N, Lanzenberger R, Asenbaum S, Dudczak R, Kasper S, Tauscher J. · Department of General Psychiatry, Medical University Vienna, Vienna, Austria. · Eur Neuropsychopharmacol. · Pubmed #16945507 No free full text.

Abstract: We explored the relationship between striatal dopamine-2 (D(2)) receptor occupancy and extra-pyramidal symptoms (EPS) in bipolar patients receiving olanzapine. Seventeen patients with a DSM-IV diagnosis of bipolar disorder were treated with 5-45 mg/day olanzapine for at least 14 days. After that period, D(2) receptor occupancy was determined using Iodobenzamide (IBZM) and SPECT. EPS were assessed by the Simpson-Angus Scale (SAS) and Barnes-Akathisia Scale (BAS). We found a dose-dependent increase in occupancy: 5 mg led to 28-50%, 10 mg to 40-68%, 15 mg to 69%, 20 mg to 57-66%, 30 mg to 66% and 45 mg to 80% D(2) receptor occupancy; and a significant correlation between plasma levels and occupancy (R(2)=.55, P=.001). Similar to schizophrenic patients, bipolar patients did not exhibit EPS at D(2) occupancy levels of 28 to 80%. Although we did not find an increased vulnerability for acute EPS in bipolar patients receiving olanzapine at clinical relevant doses, this needs to be replicated with larger sample sizes.

Pjrek E, Winkler D, Stastny J, Konstantinidis A, Heiden A, Kasper S. · Department of General Psychiatry, University Hospital for Psychiatry, Währinger Gürtel 18-20, A-1090 Vienna, Austria. · Eur Neuropsychopharmacol. · Pubmed #15163447 No free full text.

Abstract: Bright light therapy (BLT) has been proposed as treatment of choice for seasonal affective disorder (SAD). However, conventional antidepressants have also been found to be effective in this condition. We examined the psychopharmacologic medication in a clinical sample of 553 SAD patients, who had been treated with BLT, to assess the importance of drug treatment and to critically question the effectiveness of BLT. Forty-nine percent of our patients received psychopharmacologic treatment and about one third (35.4%) was treated with antidepressants, suggesting that BLT does not suffice as only antidepressant regimen for all SAD patients. Furthermore, our results show that only few patients with bipolar affective disorder were willing to accept long-term medication. Opposed to treatment guidelines, patients with several depressive episodes did not receive antidepressant maintenance medication or mood stabilizers more often than patients with only a few episodes.

Goodwin GM, Bowden CL, Calabrese JR, Grunze H, Kasper S, White R, Greene P, Leadbetter R. · Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, England, UK. · J Clin Psychiatry. · Pubmed #15096085 No free full text.

Abstract: BACKGROUND: Two clinical trials, prospectively designed for combined analysis, compared placebo, lithium, and lamotrigine for treatment of bipolar I disorder in recently depressed or manic patients. METHOD: 1315 bipolar I patients (DSM-IV) enrolled in the initial open-label phase, and 638 were stabilized and randomly assigned to 18 months of double-blind monotherapy with lamotrigine (N = 280; 50-400 mg/day fixed dose or 100-400 mg/day flexible dose), lithium (N = 167; serum level of 0.8-1.1 mEq/L), or placebo (N = 191). The primary endpoint was time from randomization to intervention for a mood episode. Data were gathered from August 1997 to August 2001. RESULTS: Lamotrigine and lithium were superior to placebo for time to intervention for any mood episode (median survival: placebo, 86 days [95% CI = 58 to 121]; lithium, 184 days [95% CI = 119 to not calculable]; lamotrigine, 197 days [95% CI = 144 to 388]). Lamotrigine was superior to placebo for time to intervention for depression (median survival: placebo, 270 days [95% CI = 138 to not calculable]; lithium, median not calculable; lamotrigine, median not calculable). Lithium and lamotrigine were superior to placebo for time to intervention for mania (median survival not calculable for any group). Results of additional analyses adjusted for index mood were similar; however, only lithium was superior to placebo for intervention for mania. There was no evidence that either active treatment caused affective switch. Adverse event analysis indicated more diarrhea (19% vs. 7%, p <.05) and tremor (15% vs. 4%, p <.05) in lithium-treated patients compared with lamotrigine-treated patients. CONCLUSIONS: Lamotrigine and lithium stabilized mood by delaying the time to treatment for a mood episode. Lamotrigine was effective against depression and mania, with more robust activity against depression. Lithium was effective against mania.

Heiden A, Schüssler P, Itzlinger U, Leisch F, Scharfetter J, Gebhardt C, Fuchs K, Willeit M, Nilsson L, Miller-Reiter E, Stompe T, Meszaros K, Sieghart W, Hornik K, Kasper S, Aschauer HN. · Department of General Psychiatry, Vienna, Austria. · Neuropsychobiology. · Pubmed #11093065 No free full text.

Abstract: The aim of the investigation was to test genes for predisposition to bipolar affective disorder. Therefore, we studied candidate genes in a sample of unrelated patients (n = 102) and healthy controls (n = 79) of Austrian origin, searching for a possible association between polymorphic DNA markers of 5 candidate genes (serotonin transporter, 5-HTT; serotonin 2a receptor, 5-HT2a; dopamine D2 receptor, DRD2; dopamine D3 receptor, DRD3; dopamine transporter, DAT1) and bipolar disorder. There was an association between allelic and genotypic frequencies of 5-HTT and affection status (p = 0.014 and p = 0.017, respectively). However, after correction for multiple comparisons (Bonferroni), these results did not remain significant. Nevertheless, the findings might suggest that alterations in the structure of 5-HTT are involved in the pathogenesis of bipolar disorder, which could have major implications in treatment. No association between 5-HT2a, DRD2, DRD3, DAT1 and bipolar disorder was found.

Schosser A, Fuchs K, Scharl T, Leisch F, Bailer U, Kasper S, Sieghart W, Hornik K, Aschauer HN. · Department of General Psychiatry, University Hospital for Psychiatry, Medical University Vienna, Austria. · Eur Neuropsychopharmacol. · Pubmed #17344034 No free full text.

Abstract: After publishing a genome scan and follow-up fine mapping, suggesting schizophrenia and bipolar disorder linkage to chromosome 3q29, we now genotyped 11 additional SNPs (single nucleotide polymorphisms), in order to narrow down a potential candidate region. Linkage was performed using the GENEHUNTER program version 2.1r3. A NPL score Z(all) of 3.891 (p=0.000156) was observed with SNP rs225. In short, we found significant linkage scores most telomeric on chromosome 3q29, spanning 3.46 Mbp (7 SNPs).

Letmaier M, Schreinzer D, Reinfried L, Glauninger G, Thierry N, Kapitany T, Kasper S. · Department of General Psychiatry, Medical University of Vienna, Austria. · Int J Neuropsychopharmacol. · Pubmed #16191207 No free full text.

Abstract: The present retrospective chart review documents the treatment practice of in-patients suffering from acute manic or hypomanic episodes, at the Department of General Psychiatry, Medical University of Vienna between 1997 and 2001. The aim of the study was to compare the efficacy of typical neuroleptics and atypical antipsychotics as add-on therapy to mood stabilizers. A total of 119 episodes of consecutively admitted patients with ICD-10-defined acute mania (n=106) or hypomania (n=13) were included in a retrospective analysis. Two subgroups were separated out of the whole patient sample according to the medication used: (a) mood stabilizer+typical neuroleptic (n=27) and (b) mood stabilizer+atypical antipsychotic (n=39). The treatment patterns of both subgroups during the first 14 d of in-patient treatment were evaluated. The therapeutic effect was measured by the Clinical Global Impression Scale (CGI). Both patient groups showed no differences on CGI at admission. Patients treated with atypical antipsychotics showed a significantly greater clinical improvement after 14 d (p<0.005) and on discharge (p<0.05) than patients treated with typical neuroleptics. Furthermore, patients treated with atypical antipsychotics developed significantly less extrapyramidal side-effects (p<0.01) and were significantly treated less often with benzodiazepines (p<0.05) during the first 14 d compared to the group receiving typical neuroleptics. Based on our evaluation and the data available in the literature atypical antipsychotics can be considered as first choice for the treatment of acute mania as add-on therapy to mood stabilizers because of their better efficacy and side-effect profile compared to typical neuroleptics.

Bailer U, Wiesegger G, Leisch F, Fuchs K, Leitner I, Letmaier M, Konstantinidis A, Stastny J, Sieghart W, Hornik K, Mitterauer B, Kasper S, Aschauer HN. · Department of General Psychiatry, University Hospital for Psychiatry, Waehringer Guertel 18-20, A-1090 Vienna, Austria. · Eur Neuropsychopharmacol. · Pubmed #15572273 No free full text.

Abstract: CLOCK was hypothesised to be related to susceptibility of affective disorders. To test subsamples of affectively disordered patients, we examined age of onset (AoO), numbers of episodes and melancholic type of clinical manifestation. Using PCR and RFLP, we investigated in patients with unipolar depression and bipolar disorder (BP) whether the CLOCK T3111C SNP is associated with affective disorders (n=102) compared to healthy controls (n=103). No differences were found either in genotype or allele frequency distributions of T3111C polymorphism between patients compared to healthy controls (p>0.2). No deviations from Hardy-Weinberg Equilibrium (HWE) were detected either in patients, or healthy controls. Results suggest that there is no association between the T3111C SNP and affective disorders in general. Data of our sample replicate prior findings of Desan et al. [Am. J. Med. Genet. 12 (2000) 418]. Subsamples of patients with high numbers of affective episodes did show some deviations in genotypes (p=0.0585).

Letmaier M, Schreinzer D, Thierry N, Wolf R, Kasper S. · Klinische Abteilung für Allgemeine Psychiatrie, Universitätsklinik für Psychiatrie, Wien, Austria. · Nervenarzt. · Pubmed #15021926 No free full text.

Abstract: The aim of the present retrospective chart analysis was to compare published treatment algorithms with the treatment patterns of 90 consecutive inpatients suffering from acute mania or hypomania at the Department of General Psychiatry, University of Vienna, from 1997 to 1999. Treatment strategies during the first 14 days and on discharge as well as sociodemographic and illness related data were evaluated. The results of our study reflect that international guidelines were not included in daily practice from 1997 to 1999 with regard to the usage pattern of atypical antipsychotics versus typical neuroleptics. Also, recommendations have not been taken into account about monotherapy with a mood stabilizer as first-line treatment for acute mania (polypharmacia was the predominant treatment scheme) and the advice to taper off benzodiazepines (at discharge).

Schosser A, Fuchs K, Leisch F, Bailer U, Meszaros K, Lenzinger E, Willinger U, Strobl R, Heiden A, Gebhardt C, Kasper S, Sieghart W, Hornik K, Aschauer HN. · Department of General Psychiatry, University Hospital for Psychiatry, A-1090 Vienna, Austria. · J Psychiatr Res. · Pubmed #15003442 No free full text.

Abstract: The present linkage study is a follow-up within the chromosome 3q29 region in schizophrenia and bipolar affective disorder families, based on our recently published genome scan, resulting in evidence for linkage of both disorders to this region (marker D3S1265: NPL [non parametric lod] score Z(all)=3.74, P=0.003). Using the same family sample (five pedigrees with schizophrenic index patients and three pedigrees with index bipolar disorder patients N=86; 50 of them were available for genotyping), genotyping of eight additional markers close to D3S1265 was done. Five of those new markers (three centromeric and two telomeric of D3S1265) spanning 4.14 cM (centiMorgan) could be used for statistical analyses ("new markers"). Moreover, marker D3S1265, genotyped within the published genome scan, was used for additional calculations. Linkage analysis was performed using the GENEHUNTER program version 2.1r3. Within newly genotyped markers the highest NPL score Z(all) observed was 1.93296 with the telomeric SNP (single nucleotide polymorphism) rs1835669, corresponding to P=0.032166. Statistical analysis including D3S1265, located in between the newly genotyped markers, resulted in a peak NPL score Z(all)=4.00179 with marker D3S1265, that is P=0.000128. Doing subset analyses of the bipolar disorder and schizophrenia families separately with new markers and D3S1265, linkage signals arose substantially from bipolar disorder families, with contribution from schizophrenia families, too. The results of our follow-up study support our previous linkage finding of schizophrenia and bipolar affective disorder to chromosome 3q29.

Willeit M, Praschak-Rieder N, Neumeister A, Zill P, Leisch F, Stastny J, Hilger E, Thierry N, Konstantinidis A, Winkler D, Fuchs K, Sieghart W, Aschauer H, Ackenheil M, Bondy B, Kasper S. · Department of General Psychiatry, University Hospital of Psychiatry, Vienna, Austria. · Mol Psychiatry. · Pubmed #14593433 No free full text.

Abstract: 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.

Winkler D, Willeit M, Wolf R, Stamenkovic M, Tauscher J, Pjrek E, Konstantinidis A, Schindler S, Barnas C, Kasper S. · Department of General Psychiatry, University Hospital for Psychiatry, Währinger Gürtel 18-20, A-1090, Vienna, Austria. · Eur Neuropsychopharmacol. · Pubmed #12650958 No free full text.

Abstract: 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.