The efficacy of lithium The main goal of treatment in patients with bipolar disorder is to prevent recurrences and suicidal acts. Of the variety of drugs now available to treat this condition, lithium has been shown to be the most efficacious in the long-term treatment of bipolar disorder. The earliest controlled studies were performed in the 1960s and demonstrated response rates of 70 to 80%. However, later studies were not always able to replicate these findings. This led to a growing critique of lithium treatment, primarily from researchers in the United States. Some US researchers also advanced the hypothesis that long-term lithium treatment would lose its efficacy over time, or after discontinuation and subsequent reinstallation. However, this hypothesis was based on preliminary findings in small patient groups and could not be replicated elsewhere. In a large sample of 163 bipolar patients on long-term lithium treatment, the IGSLI demonstrated that it was indeed possible for patients who had shown an excellent primary response to remain stable for decades, regardless of discontinuations (Grof 1999). During the 1990s, it became evident that the decrease in response rates observed previously had been due to the widespread use of lithium in naturalistic, and therefore less controlled, settings. The introduction of modern diagnostic systems (DSM III R, ICD 10) had also broadened the criteria of bipolar disorder, thus leading to a more heterogeneous group of patients. Different subtypes of bipolar disorder The IGSLI is currently working on the hypothesis that the diagnosis of bipolar subtypes may help achieve maximal response in patients on long-term treatment. When used to treat the classical type of bipolar illness (i.e. without psychiatric comorbidity and without mood-incongruent psychotic features), lithium is superior to other treatment options. However, lithium is less effective in patients with atypical bipolar disorder, which is characterised by mood-incongruent psychotic features, substance abuse, anxiety disorders or other psychiatric comorbidity, and frequently by residual non-affective symptoms between episodes. Results from several other European research groups support this hypothesis. Distinguishing between subtypes may also be useful for evaluating the prognosis of bipolar women during pregnancy. In a retrospective study, the IGSLI demonstrated that in women with typical, or type I bipolar disorder, the risk of recurrence during pregnancy was markedly lower than had been expected in light of the normal clinical course of the disease. Exploring the underlying protective mechanisms in such cases may help lead to a new understanding of the pathophysiology of affective disorders and to new approaches to treatment and prevention. The spectrum of therapeutic options has broadened since the emergence of anticonvulsants as a means of treating affective disorders. Applying lithium and anticonvulsants in a more differential manner might bring considerable benefits, especially to the large number of patients whose illness differs significantly from the classical type of bipolar disorder and who belong to the bipolar spectrum. Nevertheless, recently released, high-quality guidelines and overviews underscore the fact that lithium is still the first-line treatment in the prophylaxis of bipolar affective disorder. High-dose thyroxine research The problem of refractory recurrent affective illness deserves special attention, since a relatively high percentage of patients have a less than adequate response to standard prophylactic agents. For one decade now, the IGSLI has been engaged in research on high-dose thyroxine as an add-on therapy in refractory patients, especially in lithium-nonresponders. The “Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Levothyroxine as Add-on Therapy in Bipolar Depression" (Sponsor: The Stanley Medical Research Institute of the Stanley Foundation, Bethesda, MD, USA; Grant ID #02T-238) started recently as a cooperation of several IGSLI members and other European and US research centers: Investigators and participating study sites are: Charité University Medical Center Berlin, Germany: Michael Bauer (P.I.), Martin Schäfer, Mazda Adli, Johanna Sasse, Igor Sutej Ludwig-Maximilians-Universität Munich, Germany: Heinz Grunze; Emanuel Severus Technische Universität Dresden, Germany: Tom Bschor University Medical Center Utrecht, The Netherlands: Ralph Kupka, Willem A. Nolen University of California Los Angeles (UCLA), USA: Mark Frye, Lori Altshuler Stanford University School of Medicine, Stanford, USA: Natalie Rasgon Statistical Consultant: Michael Smolka, Central Institute of Mental Health, University Heidelberg, Germany. New Technologies to Improve Longitudinal Research in Bipolar Disorder Longitudinal studies are an optimal approach to understand the variable course and outcome of mood disorders. However, longitudinal studies have been limited by missing and unbalanced data values collected at unequal time intervals and by reliance on paper-based forms for data collection. To overcome methodological limitations, several IGSLI centers collect data for longitudinal studies using a validated computer-based system (ChronoRecord). Using software available in English, German and Spanish and being translated into Czech and Polish, patients record mood, medications, sleep, life events, and menstrual data onto a home computer every day. Weight is entered weekly. This technology facilitates compilation of data from multiple IGSLI centers into a large database for analysis. Automation of data collection can reduce missing data, eliminate errors associated with data entry and allows the use of familiar statistical techniques for analysis. Additionally, ongoing feedback is provided for patients and researchers in the form of graphical mood charts and statistical analyses. For more information on ChronoRecord visit www.chronorecord.org. top >>