Bipolar Disorder: Vestergaard P

Licht RW, Vestergaard P, Kessing LV, Larsen JK, Thomsen PH, Anonymous00236. · Mood Disorders Research Unit, Aarhus University Psychiatric Hospital, Risskov, Denmark. · Acta Psychiatr Scand Suppl. · Pubmed #12974784 No free full text.

Abstract: A subcommittee under the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark have recently developed national guidelines for the psychopharmacological treatment with lithium and antiepileptic drugs, and the present translation aims at contributing to the international discussion on the development of proper guidelines for the treatment of bipolar disorder. Among the antiepileptic drugs, the report deals with valproate, carbamazepine and lamotrigine and to a lesser extent with oxcarbazepine, gabapentin and topiramate. The various drugs will be reviewed, outlining the scientific evidence for mood-stabilizing properties and discussing major side effects, the most important interactions with other drugs and practical use. Special considerations during pregnancy and lactation, during treatment of children and adolescents and during treatment of the elderly will also be presented. Antidepressants and antipsychotics are beyond the scope of the report, but due to the mood-stabilizing properties of at least some of the atypical antipsychotics, these agents will be brought into some focus in connection with the overall treatment guidelines for the different phases of bipolar disorder given at the end of this report.

Vestergaard P. · The Central Unit, Aarhus University Psychiatric Hospital, Risskov, Denmark. · Bipolar Disord. · Pubmed #15541067 No free full text.

Abstract: Practice policies and guidelines for the long-term management of bipolar patients have appeared in many parts of Europe and North America. Although recommendations in most areas do concur remarkable differences are apparent both regarding diagnostic practice and pharmacological management. Differences among recommendations point towards professional and cultural differences between Europe and North America but also towards areas with unresolved research questions and lack of scientific evidence.

Vestergaard P, Licht RW. · Mood Disorders Research Unit, Aarhus University Psychiatric Hospital, Skovagervej 2, 8240 Risskov, Denmark. · World J Biol Psychiatry. · Pubmed #12587181 No free full text.

Abstract: Lithium has been used as a treatment for various psychiatric- and somatic-illnesses for more than 50 years. Today the main use of lithium is for the prevention of episode recurrences in bipolar disorder. The main emphasis of this review will be on the efficacy and effectiveness of lithium prophylaxis in bipolar disorder but the review will also discuss other indications for lithium treatment, the historical development, pharmacokinetic and -dynamic issues, unwanted effects of lithium and the organisation of treatment services. Finally, although not the main purpose of this review, a short description of alternative mood stabilizing drugs will also be presented.

Licht RW, Vestergaard P. · Forskningsafdeling for affektive sygdomme, Psykiatrisk Hospital i Arhus, Arhus Universitetshospital, DK-8240 Risskov. · Ugeskr Laeger. · Pubmed #12025705 No free full text.

Abstract: This paper gives an update on the psychopharmacological treatment of bipolar disorder. The antimanic efficacy of lithium is well documented. The same applies to valproate, which is also efficacious in mixed mania. Conventional antipsychotics act fast in mania and do not require blood tests, but they have considerable neurological side effects. The newer antipsychotics, olanzapine, risperidone, and ziprasidone, have also been shown to have antimanic efficacy. Clozapine is extremely effective, also when other treatment fails. For the treatment of bipolar depression, lithium, lamotrigine, and antidepressants all seem to work, but antidepressants may sometimes precipitate mania or worsen the course of illness. For prophylaxis, lithium is still to be considered the first drug of choice. However, for several reasons, for instance treatment failure or side effects, long-term treatment with antiepileptics may often be necessary. Among the antiepileptics, carbamazepine, valproate, and lamotrigine are the best studied.

Licht RW, Vestergaard P, Brodersen A. · Mood Disorders Research Unit, Aarhus University Psychiatric Hospital, Risskov, Denmark. · Bipolar Disord. · Pubmed #18199244 No free full text.

Abstract: OBJECTIVES: From placebo-controlled studies of up to two years duration, it has been established that lithium has preventive efficacy in bipolar disorder (BD). However, the effectiveness of lithium under routine conditions seems less pronounced. In the present study, the overall 15.3-year outcome in BD patients commenced on lithium is described. METHODS: Ninety-one patients with BD consecutively commenced on prophylactic lithium treatment during hospitalization at the Aarhus University Psychiatric Hospital from 1981 to 1983 were followed until death or censoring occurred during up to 15.3 years of observation. Register-based outcome measures, available for all patients, included accumulated duration of admission and number of admissions. In addition, serious attempts were made to collect detailed information on treatment during follow up. Simple descriptive statistics were applied; potential independent associations between baseline variables and outcome were examined using logistic regression models. RESULTS: Of the 91 patients, 27 patients died (six from suicide) during the observation period, which was an excess mortality compared to the general population. Fifty percent of the patients were admitted for more than one month per 20 months of observation and admitted more than once for each four years of observation. Only 19 (21%) patients were not admitted to hospital during the observation period. No statistically significant predictors of poor outcome could be identified. In addition to lithium prophylaxis given for variable lengths of time, the majority of the 36 (40%) patients, from whom treatment data were available, received various other drug treatments during follow-up. CONCLUSIONS: The overall outcome in patients beginning prophylactic treatment is unsatisfactory. However, due to the observational design and the lack of detailed treatment information during the long follow-up period, inferences about the efficacy of lithium cannot be made from this study.

Nielsen JB, Vestergaard P. · Holstebro Sygehus, Neurologisk Afdeling. · Ugeskr Laeger. · Pubmed #17303036 No free full text.

Abstract: A 64-year-old woman with bipolar disorder had received treatment with lithium for 33 years when she was admitted to the Department of Neurology with clinical signs and symptoms of an apoplectic insult. Her serum lithium level was 2.42 mmol/l. She was treated conservatively with electrolyte solutions and diuretics. Hemodialysis was judged unnecessary, and the patient recovered after 11 days. Patients given long-term lithium treatment should be instructed about risk factors, and their serum lithium and serum creatinine levels should be monitored regularly in order to prevent intoxication.

Brodersen A, Licht RW, Vestergaard P, Olesen AV, Mortensen PB. · Psykiatrisk Hospital, Arhus Universitetshospital, DK-8240 Risskov. · Ugeskr Laeger. · Pubmed #11816921 No free full text.

Abstract: INTRODUCTION: Lithium treatment is claimed to reduce mortality in patients with affective disorder, but the evidence is conflicting. The aim of this study was to estimate mortality rates from a cohort of such patients, who commenced treatment with lithium, over an observation period of 16 years. MATERIAL AND METHODS: The mortality rates of affectively ill patients, who commenced lithium treatment, were compared with the mortality rates in the general Danish population, standardised for age, sex, and a time to death from all causes, suicide, and cardiovascular death. Comparison of the time from a two-year follow-up to death from any cause between patients compliant and non-compliant with two years of lithium treatment was performed with the Cox regression analysis. RESULTS: Forty of the 133 patients who participated in the study died during the 16-year observational period; 11 from suicide. Mortality in the patients was twice that of the background population. This statistically significantly higher mortality was predominantly caused by the number of suicides, whereas mortality from all other causes was similar to the background population. Thirty-two patients died after the first two years of observation and were included in the analysis of association between death and two years of compliance with lithium. Suicide occurred more frequently in the lithium non-compliant patients than in the lithium compliant patients. DISCUSSION: Mortality, particularly death from suicide, was significantly increased in unselected affective disorder patients, who commenced lithium treatment, as compared with the background population.

Licht RW, Vestergaard P, Rasmussen NA, Jepsen K, Brodersen A, Hansen PE. · Mood Disorders Research Unit, Aarhus University Psychiatric Hospital, Skovagervej 2, DK-8240 Risskov, Denmark. · Acta Psychiatr Scand. · Pubmed #11722321 No free full text.

Abstract: OBJECTIVE: This paper describes the outcome for the first 148 patients referred to a lithium clinic. METHOD: Two-year follow-up data from treatment charts are reported for all patients entering a lithium clinic in the study period. RESULTS: Lithium was given as the only mood stabilizer in 132 (89.2%) of the cases. Thirty-two (21.6%) patients were readmitted with a new affective disorder episode. Twenty-nine (19.6%) patients discontinued treatment prematurely. Variables predicting the recurrence of new affective disorder episodes as well as premature discontinuation of treatment were identified. CONCLUSION: The majority of bipolar patients received lithium for prophylaxis against recurrent affective disorder episodes. The outcome was moderate but comparable to the 30-40% improvement usually reported in follow-up studies of bipolar patients given long-term prophylactic treatment with lithium. Better long-term treatment results for bipolar patients depend on both the development of more effective mood stabilizing drugs or drug combinations and the improvement of patients' adherence to treatment.

Duffy A, Turecki G, Grof P, Cavazzoni P, Grof E, Joober R, Ahrens B, Berghöfer A, Müller-Oerlinghausen B, Dvoráková M, Libigerová E, Vojtĕchovský M, Zvolský P, Nilsson A, Licht RW, Rasmussen NA, Schou M, Vestergaard P, Holzinger A, Schumann C, Thau K, Robertson C, Rouleau GA, Alda M. · Department of Psychiatry, Dalhousie University, Halifax. · J Psychiatry Neurosci. · Pubmed #11022400 links to  free full text

Abstract: OBJECTIVE: To test for genetic linkage and association with GABAergic candidate genes in lithium-responsive bipolar disorder. DESIGN: Polymorphisms located in genes that code for GABRA3, GABRA5 and GABRB3 subunits of the GABAA receptor were investigated using association and linkage strategies. PARTICIPANTS: A total of 138 patients with bipolar 1 disorder with a clear response to lithium prophylaxis, selected from specialized lithium clinics in Canada and Europe that are part of the International Group for the Study of Lithium-Treated Patients, and 108 psychiatrically healthy controls. Families of 24 probands were suitable for linkage analysis. OUTCOME MEASURES: The association between the candidate genes and patients with bipolar disorder versus that of controls and genetic linkage within families. RESULTS: There was no significant association or linkage found between lithium-responsive bipolar disorder and the GABAergic candidate genes investigated. CONCLUSIONS: This study does not support a major role for the GABAergic candidate genes tested in lithium-responsive bipolar disorder.

Vestergaard P, Licht RW. · Arhus Universitetshospital, Psykiatrisk Hospital, afdeling A. · Ugeskr Laeger. · Pubmed #10895597 No free full text.

This publication has no abstract.

Alda M, Turecki G, Grof P, Cavazzoni P, Duffy A, Grof E, Ahrens B, Berghöfer A, Müller-Oerlinghausen B, Dvoráková M, Libigerová E, Vojtĕchovský M, Zvolský P, Joober R, Nilsson A, Prochazka H, Licht RW, Rasmussen NA, Schou M, Vestergaard P, Holzinger A, Schumann C, Thau K, Rouleau GA. · Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. · Am J Med Genet. · Pubmed #10893493 No free full text.

Abstract: Corticotropin-releasing hormone (CRH) and proenkephalin (PENK) are hypothalamic peptides involved in the stress response and hypothalamic-pituitary axis regulation. Previous research has implicated these peptides in the pathogenesis of affective disorders. In this study we investigated two polymorphisms located in the genes that code for CRH and PENK by means of association and linkage analyses. A total of 138 bipolar patients and 108 controls were included in the association study. In addition, 24 families were available for linkage analysis, including six families of probands with documented periodic positivity of dexamethasone suppression tests (DST) during remission. We found no association of bipolar disorder with either gene. Similarly, we did not find any evidence of linkage (P = 0.56 for CRH and 0.52 for PENK) in the entire sample or in the subsample of families of DST positive probands. In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribute to the genetic susceptibility to bipolar disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:178-181, 2000.

Turecki G, Alda M, Grof P, Joober R, Lafrenière R, Cavazzoni P, Duffy A, Grof E, Ahrens B, Berghöfer A, Müller-Oerlinghausen B, Dvoráková M, Libigerová E, Vojtechovský M, Zvolský P, Nilsson A, Prochazka H, Licht RW, Rasmussen NA, Schou M, Vestergaard P, Holzinger A, Schumann C, Thau K, Rouleau GA. · Centre for Research in Neuroscience, The Montreal General Hospital, McGill University, 1650 Cedar Ave, Montreal, Canada. · J Affect Disord. · Pubmed #10760559 No free full text.

Abstract: BACKGROUND: Several studies have suggested that expanded trinucleotide repeats, particularly CAG, may have a role in the etiology of BD. Results obtained with the repeat expansion detection technique (RED) have indicated that bipolar patients have an excess of expanded CAG repeats. However, it is not clear which loci account for this difference. METHODS: Using lithium-responsive bipolar patients in order to reduce heterogeneity, we investigated five loci that are expressed in the brain and contain translated CAG repeats. A sample of 138 cases and 108 controls was studied. Genotypes were coded quantitatively or qualitatively and repeat distributions were compared. RESULTS: No difference was found in allele distribution between cases and controls for any of the loci studied. In one locus - L10378 - patients had a tendency to present shorter alleles (28.1 versus 27.9 repeats; t=2.55, df=205, P=0.011), however, this difference disappeared after correction for multiple testing. LIMITATIONS: The study has limitations common to most candidate gene association studies, that is, limited number of loci investigated and limited power to detect loci that account for a small proportion of the total genetic variability. CONCLUSIONS: Our results suggest that the loci investigated have no major role in the genetic predisposition to bipolar disorder.

Turecki G, Grof P, Cavazzoni P, Duffy A, Grof E, Ahrens B, Berghöfer A, Müller-Oerlinghausen B, Dvoráková M, Libigerová E, Vojtechovsky M, Zvolsky P, Joober R, Nilsson A, Prochazka H, Licht RW, Rasmussen NA, Schou M, Vestergaard P, Holzinger A, Schumann C, Thau K, Rouleau GA, Alda M. · Centre for Research in Neuroscience, Montreal General Hospital, McGill University, Canada. · Psychiatr Genet. · Pubmed #10335547 No free full text.

Abstract: A number of association studies have investigated the role of the monoamine oxidase A (MAOA) gene in the susceptibility to bipolar disorder. Although some studies have reported positive findings, there remains some controversy, because results from different studies have not been consistent. A common explanation for inconsistencies between studies is genetic heterogeneity. We have focused on lithium responsive bipolar disorder as a way to reduce heterogeneity. In this study, we investigated the role of MAOA in lithium responsive bipolar patients using association and linkage study designs. The investigation used 138 patients and 108 normal controls. In addition, 25 families were also studied. Our results were not supportive of a major role of MAOA in the predisposition to bipolar disorder.

Turecki G, Alda M, Grof P, Joober R, Cavazzoni P, Duffy A, Grof E, Ahrens B, Berghöfer A, Müller-Oerlinghausen B, Dvoráková M, Libigerová E, Vojtechovský M, Zvolský P, Nilsson A, Prochazka H, Licht RW, Rasmussen NA, Schou M, Vestergaard P, Holzinger A, Schumann C, Thau K, Rouleau GA. · No affiliation provided · Mol Psychiatry. · Pubmed #10395210 No free full text.

This publication has no abstract.