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Biomedical subjects

R W Licht

Publications and source records attributed to R W Licht.

At least 19 recordsLinked to original sources
PubMed2005

Validation of the Bech-Rafaelsen Melancholia Scale and the Hamilton Depression Scale in patients with major depression; is the total score a valid measure of illness severity?

OBJECTIVE: Evaluation of antidepressant drug efficacy requires adequate rating scales for measuring the severity of depression. However, to measure the illness severity by such a total score, the scale needs to fulfil criteria of unidimensionality. On this background, we aimed at comparing the unidimensionality of the Bech-Rafaelsen Melancholia Scale (MES) and the 17-item Hamilton Depression Rating Scale (HAM-D(17)). METHOD: A total of 1629 patients aged between 18 and 65 years with a major depressive episode were treated openly with sertraline at a fixed oral dose of 50 mg daily during 4 weeks. The HAM-D(17) and the MES were applied at baseline and at weeks 2 and 4. Unidimensionality was tested with Mokken and Rasch analysis. RESULTS: Unidimensionality of the HAM-D(17) could not be confirmed. However, the 6-item Hamilton Depression Subscale (HAM-D(6)), was accepted by the Rasch analysis both at baseline and after 2 and 4 weeks of therapy. For the MES (as well as for the HAM-D(6)), a Loevinger coefficient of homogeneity above 0.40 (suggesting acceptance) was found at week 4. CONCLUSION: The HAM-D(6) and the MES did fulfil criteria for unidimensionality while the HAM-D(17) did not. Therefore, the extended use of the HAM-D(17) in drug trials may be questioned.

Adolescent↗
PubMed2003

Chronic lithium treatment with or without haloperidol fails to affect the morphology of the rat cerebellum.

We used unbiased stereological principles to determine whether long-term administration of lithium at human therapeutic levels, with or without haloperidol, affects the number or sizes of cerebellar Purkinje cells or the volume of histological layers in the rat cerebellum. Twenty-eight rats were randomly divided into three groups, receiving either no treatment, lithium, or lithium combined with haloperidol. The serum lithium levels ranged from 0.50 to 0.77 mmol/l. Haloperidol was given at a daily dose of 1 mg/kg. After 30 weeks of treatment, the animals were killed and the cerebelli were histologically prepared. No statistically significant differences were observed between the groups with respect to the cerebellar measures.

Animals↗
PubMed2003

Psychopharmacological treatment with lithium and antiepileptic drugs: suggested guidelines from the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark.

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.

Adolescent↗
PubMed2001

[Mortality in patients with affective disorder who commenced treatment with lithium. A 16-year follow-up].

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.

Adolescent↗
PubMed2001

Limitations in randomised controlled trials evaluating drug effects in mania.

Considering the increasing number of drugs evaluated for mania in randomised controlled trials (RCTs) and the potential discrepancies between recommendations based on RCTs and the antimanic treatment given in clinical practice, this paper addresses some issues related to RCTs on drug effects in mania. One major question raised in the paper is to what extent selection prior to the point of randomisation in RCTs in mania may limit the applicability of study results to patients seen in ordinary clinical practice. Although such limitations in generalisability can be difficult to investigate empirically, it is emphasised that they should be openly discussed in the reports of RCTs. Another major focus is the issue of evaluation and interpretation of outcome, including a discussion of various response criteria based on mania rating scale scores. It is pointed out that essential criteria of dimensionality have only been sufficiently evaluated for the Bech-Rafaelsen Mania Rating Scale, although the fulfilment of such criteria are prerequisites for adding up the item scores to a total score reflecting the severity of mania. It is suggested that response defined as a decline in mania score below a certain limit may have some advantages over the commonly used 50% reduction criterion. The issues arising from the unusual high drop-out rates of around 50% are also addressed. Despite the fact that we need rigorous placebo-controlled trials to establish antimanic efficacy of new compounds, we also need large scale pragmatic studies using broad inclusion criteria, comparing the various treatments, alone or in combination, to investigate how they work in clinical practice. These studies maybe randomised but open and use simple but relevant outcome measures.

Antimanic Agents↗
PubMed2001

A lithium clinic for bipolar patients: 2-year outcome of the first 148 patients.

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.

Adult↗
PubMed2001

Fixed-dosed risperidone in mania: an open experimental trial.

The purpose of the study was to assess the efficacy and tolerance of risperidone in mania. Fourteen inpatients with a DSM-IV manic episode were treated with risperidone at a fixed daily dose of 6 mg for 4 weeks. Compliance was assured by weekly determinations of serum concentrations of risperidone. Ten out of the 14 patients completed all 4 weeks of treatment, and all of these achieved at least a 75% reduction on the Bech-Rafaelsen Mania Scale (MAS). On the other applied measures, a substantial improvement was also seen in most patients, and no worsening in any of the rating scales was observed in any patient. Five patients continued concomitant treatment with a mood stabilizer. When the results were compared with the results from a similar historic control group treated with the middle-potency typical antipsychotic zuclopenthixol at a daily dose of 20 mg under the same experimental conditions, a between group difference in mean percentage change (baseline versus endpoint) on the MAS was 34.7% (95% confidence interval = 7.9-61.6%) in favour of risperidone. Side-effect profiles were rather similar in the two treatment groups. Despite design limitations, these findings may justify the conduction of randomized controlled trials to investigate the use of risperidone in mania.

Administration, Oral↗
PubMed2001

50 Years with lithium treatment in affective disorders: present problems and priorities.

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.

Bipolar Disorder↗
PubMed2000

Association and linkage studies of CRH and PENK genes in bipolar disorder: a collaborative IGSLI study.

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.

Adult↗
PubMed2000

Polyglutamine coding genes in bipolar disorder: lack of association with selected candidate loci.

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.

Adult↗
PubMed2000

Sixteen-year mortality in patients with affective disorder commenced on lithium.

BACKGROUND: Lithium treatment is claimed to reduce mortality in patients with affective disorder, but the evidence is conflicting. AIM: To estimate mortality rates from a cohort of patients with affective disorder commenced on lithium with an observation period of two years and a follow-up after 16 years. METHOD: The mortality rates of patients were compared with those of the general Danish population, standardised for age, gender and calendar time with respect to death from all causes, suicide and death from cardiovascular disease. RESULTS: Forty of the study's 133 patients died during the 16-year observation period (11 from suicide). Mortality among patients commenced on lithium was twice that of the general population. The statistically significantly elevated mortality was due largely to an excess of suicides; mortality from all other causes was similar to the background populations. Thirty-two patients died after the first two years of observation and were included in the analysis of the association between death and treatment compliance. Suicide occurred more frequently among those patients not complying with treatment. CONCLUSION: Mortality, especially suicide, was significantly increased in unselected patients with affective disorder commenced on lithium relative to the general population.

Adult↗
PubMed2000

Association and linkage studies of candidate genes involved in GABAergic neurotransmission in lithium-responsive bipolar disorder.

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.

Alleles↗
PubMed1999

MAOA: association and linkage studies with lithium responsive bipolar disorder.

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.

Alleles↗
PubMed1998

[May results from randomized clinical trials be generalized? An example from psychopharmacology].

Exemplified by a randomized trial on antimanic treatment, this paper addresses the question whether selection of patients for drug trials may limit the applicability of study results from the randomized patients to a wider population. During a two-year period, all consecutively admitted patients from a defined catchment area were screened for fulfilling the inclusion criteria concerning age, diagnosis and severity of illness. The subsequently excluded subgroups of patients were compared with the randomized patients by means of multivariate data analysis. One hundred and sixty four patients met the inclusion criteria. However, after exclusion for various reasons, only 27 (17%) patients remained for randomization. The randomized patients and the excluded patients differed substantially. The generalizability of trial results is limited. Reports of randomized drug trials should carefully describe the screening procedure for inclusion, and, when possible, present relevant comparisons between the randomized patients and the various subgroups of patients meeting the exclusion criteria.

Adult↗
PubMed1998

Evidence for a role of phospholipase C-gamma1 in the pathogenesis of bipolar disorder.

Several studies have indicated that patients with bipolar disorder (BD) who respond well to lithium prophylaxis constitute a biologically distinct subgroup. Lithium is thought to stabilize mood by acting at the phosphoinositide cycle. We have investigated a polymorphism located in the gene (PLCG1) that codes for a gamma-1 isozyme of phospholipase (PLC), an enzyme that plays an important role in the phosphoinositide second messenger system. A population-based association study and a family-based linkage study were carried out on patients who were considered excellent responders to lithium prophylaxis. Response to lithium was evaluated prospectively with an average follow-up of 14.4 +/- 6.8 years. The PLCG1 polymorphism was investigated in 136 excellent lithium responders and 163 controls. In addition, the segregation of this marker was studied in 32 families ascertained through lithium-responsive bipolar probands. The allele distributions between lithium-responsive bipolar patients and controls were different, with a higher frequency of one of the PLCG1 polymorphisms in patients (chi2 = 8.09; empirical P = 0.033). This polymorphism, however, confers only a small risk (OR = 1.88, CI 1.19-3.00). Linkage studies with the same marker yielded modest support for the involvement of this gene in the pathogenesis of BD when unilineal families were considered (Max LOD = 1.45; empirical P = 0.004), but not in the whole sample. Our results provide preliminary evidence that a PLC isozyme may confer susceptibility to bipolar disorder, probably accounting for a fraction of the total genetic variance. Whether this polymorphism is implicated in the pathogenesis of BD or in the mechanism of lithium response remains to be determined.

Adult↗