Anne Berghöfer

Obesity prevalence from a European perspective: a systematic review

BackgroundObesity has been recognised as an important contributing factor in the development of various diseases, but comparative data on this condition are limited. We therefore aimed to identify and discuss current epidemiological data on the prevalence of obesity in European countries.MethodsWe identified relevant published studies by means of a MEDLINE search (1990–2008) supplemented by information obtained from regulatory agencies. We only included surveys that used direct measures of weight and height and were representative of each countrys overall population.ResultsIn Europe, the prevalence of obesity (body mass index ≥ 30 kg/m2) in men ranged from 4.0% to 28.3% and in women from 6.2% to 36.5%. We observed considerable geographic variation, with prevalence rates in Central, Eastern, and Southern Europe being higher than those in Western and Northern Europe.ConclusionIn Europe, obesity has reached epidemic proportions. The data presented in our review emphasise the need for effective therapeutic and preventive strategies.

Health-economic burden of obesity in Europe

Although overweight and obesity have long been recognised as major risk factors for a number of chronic diseases, lifestyle developments have led to substantial increases in bodyweight worldwide. In addition to their negative effects on health and quality of life, obesity and associated comorbidities may have a considerable impact on healthcare expenditures. The aim of this systematic review was to summarise cost estimates and compare costs attributable to obesity across different European countries. A structured search in MEDLINE, EMBASE, and all EBM Reviews was conducted to identify relevant literature. Two researchers independently assessed publications according to pre-defined inclusion criteria and with regard to study methodology. Costs attributable to obesity were extracted from the included studies and calculated relative to country-specific gross domestic income. Out of 797 publications that met our search criteria, 13 studies investigating 10 Western European countries were determined to be relevant and included in our review. Obesity-related healthcare burdens of up to 10.4 billion euros were found. Reported relative economic burdens ranged from 0.09% to 0.61% of each country’s gross domestic product (GDP). Obesity appears to be responsible for a substantial economic burden in many European countries, and the costs identified in the available studies presumably reflect conservative estimates. There remains a great need for prospective and standardised studies to provide more accurate estimates of costs for all European countries.

Evidence for a role of phospholipase C-γ1 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 stablize mood by acting at the phosphoinositide cycle. We have investigated a polymorphism located in the gene (PLCG1) that codes for a γ-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 (χ2 = 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.

Non-adherence with long-term prophylaxis: a 6-year naturalistic follow-up study of affectively ill patients.

In a retrospective 6-year follow-up, we assessed the reasons for and the frequency and consequences of non-adherence in 76 affectively ill patients receiving lithium prophylaxis in two lithium clinics. Thirty-eight bipolar (50%), 21 unipolar (27.6%) and 17 schizoaffective patients (22.4%) diagnosed according to DSM-III-R, were investigated with a specialized follow-up documentation. Of the patients 53.9% discontinued prophylaxis at some time; 43.2% of the discontinuations occurred during the first 6 months. In contrast to other studies the main reason reported for non-adherence was resistance against long-term treatment. According to the Lithium Attitudes Questionnaire non-adherent patients showed significantly less acceptance of the prophylaxis in general, of the effectiveness of lithium and of the severity of their illness than adherent patients. In a multivariate analysis of various parameters, only the negative attitude to prophylaxis correlated significantly with non-adherence. Significant correlation was found between treatment outcome and duration of initial prophylaxis. During the 6-year follow-up only the adherent patients showed a significant reduction of the number and duration of admissions. Our findings confirmed non-adherence as a major problem in the effectiveness of lithium prophylaxis. The authors recommend prospective investigations of attitudes and the impact of psychoeducation on long-term adherence.

Lithium augmentation therapy in refractory depression-update 2002.

Abstract.Lithium has been used to augment the efficacy of antidepressant medications for more than 20 years. The present study examines whether evidence exists to support the clinical efficacy of lithium augmentation in refractory, treatment resistant depression. Studies were identified by searching Medline (1980 to August 2002) and by scanning the references of published reviews and standard textbooks. Studies were selected if they were open-labeled or double-blind, placebo-controlled or comparator trials that involved patients who had not responded to conventional antidepressants. 27 prospective studies were identified that included a total of 803 depressed patients displaying the following designs: 10 double-blind, placebo-controlled trials, 2 randomized, double-blind comparator trials, 2 randomized, open comparator trials, and 13 open-label trials. The majority of randomized controlled trials has demonstrated substantial efficacy of lithium augmentation in partial and non responders to antidepressant treatment. In the placebo-controlled trials, the response rate in the lithium group was 45% and in the placebo group 18% (p<0.001). Summarizing all open and controlled studies, approximately 50% of patients responded to lithium augmentation within 4 weeks. In conclusion, lithium is the foremost and most well-documented augmentation strategy in refractory depression.Therefore, it should be considered a first-line treatment strategy in patients with major depression who do not adequately respond to standard antidepressants.

Lithium Augmentation Therapy in Refractory Depression: Clinical Evidence and Neurobiological Mechanisms

Objective: This systematic review examines the evidence and discusses the clinical relevance of lithium augmentation as a treatment strategy for refractory major depressive episodes. It also examines hypotheses on the mode of action of lithium augmentation, with a focus on serotonin (5-HT) and neuroendocrine systems, and proposes recommendations for future research. Method: We searched the Medline computer database and the Cochrane Library for relevant original studies published in English from January 1966 to February 2003. The key words were as follows: lithium, augmentation strategies, lithium augmentation, major depression, refractory depression, treatment-resistant depression, neuroendocrinology, and serotonin. Results: Of 27 prospective clinical studies published since 1981, 10 were double-blind, placebo-controlled trials, 4 were randomized comparator trials, and 13 were open-label trials. Five of 9 acute-phase placebo-controlled trials demonstrated that lithium augmentation had substantial efficacy. In the acute-treatment trials, the average response rate in the lithium group was 45%, and in the placebo group, 18% (P < 0.001). One placebo-controlled trial showed the efficacy of lithium augmentation in the continuation-phase treatment. Summarizing the open and controlled data, approximately 50% of patients responded to lithium augmentation within 2 to 6 weeks. Animal studies offer robust evidence that lithium augmentation increases 5-HT neurotransmission, possibly by a synergistic action of lithium and the antidepressant on brain 5-HT pathways. Conclusions: Augmentation of antidepressants with lithium is the best-documented augmentation therapy in the treatment of refractory depression. Emerging data from animal studies suggest that the 5-HTergic system is involved in the augmentatory effect of lithium.

The Impact of Lithium Long-Term Medication on Suicidal Behavior and Mortality of Bipolar Patients

ABSTRACT The article reviews the existing evidence and the concept of the anti-suicidal effect of lithium long-term treatment in bipolar patients. The core studies supporting the concept of a suicide preventive effect of lithium in bipolar patients come from the international research group IGSLI, from Sweden, Italy, and recently also from the U.S. Patients on lithium possess an eight- time lower suicide risk than those off lithium. The anti-suicidal effect is not necessarily coupled to lithiums episode suppressing efficacy. The great number of lives potentially saved by lithium adds to the remarkable benefits of lithium in economical terms. The evidence that lithium can effectively reduce suicide risk has been integrated into modern algorithms in order to select the optimal maintenance therapy for an individual patient.

Supraphysiological Doses of L-Thyroxine in the Maintenance Treatment of Prophylaxis-Resistant Affective Disorders

This prospective open-label study examined the efficacy of adjunctive supraphysiological doses of L-thyroxine (T4) in the maintenance treatment of prophylaxis-resistant affective disorder. Twenty-one (16 women, 5 men) of 25 patients enrolled consecutively over an 8-year period on the basis of their status of prophylaxis resistance (defined as two or more failures to standard prophylactic trials) participated for more than four months in the study and were eligible for the intention-to-treat analysis. The mean length of adjunctive treatment with T4 was 51.4 ± 21.7 months. The mean T4 dose at study end was 378.6 ± 90.2 μg/d. The number of episodes and hospitalizations, and the morbidity indices during the time of prophylactic T4 treatment, were compared with those measured for the same length of time before the start of T4 treatment (mirror-image method). On the Clinical Global Impression for Bipolar Disorder scale (CGI-BP, Change from Worst Phase of Illness), eleven subjects (52.4%) were rated as “very much improved”, four (19%) as “much improved”, two (9.5%) as “minimally improved” and four (19%) as “no change.” The mean total number of recurrences (8.6 before T4 treatment vs. 2.8 during T4 treatment; p = .004), the number of hospitalizations (3.1 vs. 1.9; p = .026) and the Morbidity Index (MITotal = 0.71 vs. MITotal = 0.28; p < .001) significantly declined during T4 treatment. Subjects with bipolar disorder (n = 13) benefited more from the T4 treatment intervention than did subjects with unipolar major depressive disorder (n = 4) and schizoaffective disorder (n = 4). In conclusion, adjunctive treatment with L-thyroxine in supraphysiological doses may be an effective strategy in the maintenance treatment of patients with prophylaxis-resistant affective disorders.

Course of illness and pattern of recurrences in patients with affective disorders during long-term lithium prophylaxis : a retrospective analysis over 15 years

Berghöfer A, Kossmann B, Müller‐Oerlinghausen B. Course of illness and pattern of recurrences in patients with affective disorders during long‐term lithium prophylaxis: a retrospective analysis over 15 years.

Serotonergic platelet variables in unmedicated patients suffering from major depression and healthy subjects Relationship between 5HT content and 5HT uptake

The dependence of platelet-5HT content on apparent kinetic parameters of 5HT uptake was analyzed in 56 healthy subjects and 47 depressed patients, who had not been taking psychotropic medication for several months. There were no significant relationships between apparent Vmax or Km and platelet-5HT content in both groups. However, the ratio of Vmax to Km, as a measure of apparent 5HT uptake efficiency, significantly correlated with the platelet-5HT concentration in healthy subjects (r=0.627 p<0.001). Female controls showed a higher correlation coefficient (r=0.723) than male controls (r=0.457). A marked deviation from the linear relationship between 5HT content and the ratio Vmax/K was observed in female depressed patients (r=0.250 n.s.). In male depressed patients the correlation coefficient (r=0.485 p<0.05) was similar to male healthy subjects, but the regression equations differed significantly in slope and intercept. Dividing controls and patients in subgroups with low, median and high net uptake rates, it was found that the frequencies of these uptake rate classes were 24.6%, 33.3%, 42.1% in controls and 38.3%, 44.7%, 17.0% in patients respectively. Patients and controls with low net uptake rate showed very similar uptake kinetics and uptake efficiencies, but the lack of a significant correlation between 5HT content and the ratio Vmax/Km differentiated patients from controls. The status of the serotonergic system, expressed as relationship between 5HT content and uptake efficiency, was very similar in patients and controls in the range of medium net uptake rate. A trend toward higher values of uptake efficiency was apparent in patients with high net uptake rate but the platelet-5HT content was similar to corresponding controls. Mean scores on the HAMD scale (total score and psychic anxiety item) were significantly higher in the low net uptake rate group of patients than in those with a high net uptake rate.