Article
Possible relationship between electroencephalogram finding and lithium response in bipolar disorder

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Abstract

The relationship between electroencephalogram (EEG) finding and lithium response was retrospectively examined in 58 patients with bipolar disorder. All necessary information was obtained from the clinical charts. The patients were categorized into two groups (responder or nonresponder) with regard to the lithium response and into three groups (normal, borderline, or abnormal) concerning the EEG finding. The information both on EEG and lithium response could be obtained from 27 patients. Only five cases were classified as lithium responders. None of these five responders had abnormal EEG finding, while all of five patients with abnormal EEG finding were categorized into nonresponder. No statistically significant interaction was detected between EEG finding and lithium response. This retrospective study suggests that epileptiform EEG abnormality is worth studying further as a possible predictor of lithium resistance in bipolar disorder.

Introduction

When lithium established its status as the mood stabilizer in the 1960s, a new era of pharmacological treatment for bipolar disorder has come. Despite the appearance of other mood stabilizers, lithium prophylaxis is still the first treatment of choice for bipolar disorder. However, only half of the patients with bipolar disorder show complete response to lithium treatment. Other patients show partial or no response to lithium prophylaxis and need other mood stabilizers. Therefore, if we can predict lithium response before initiation of treatment and prescribe an appropriate mood stabilizer, prognosis of bipolar disorder should be considerably improved.

Many clinical researches on predictors of lithium response were published. As predictors of positive lithium response, euphoric mood, small number of episodes, mania–depression-free interval pattern of the course of illness, and positive family history have been reported. On the other hand, as predictors of poor lithium response, mixed states, psychotic features, depression–mania-free interval pattern, rapid cycling, and high neuroticism scores have been confirmed Carroll, 1979, Maj et al., 1989, Tondo et al., 2001.

There are few reports of pharmacological and biological predictors of lithium response. Possible relationship of positive lithium response with high red blood cell/plasma lithium ratio (Mendels and Frazer, 1973) is most studied. However, the results are still controversial. There were several positive Cazzullo et al., 1975, Casper et al., 1976, Mendels et al., 1976, Swann et al., 1987, Hitzemann et al., 1989, Harvey and Kay, 1991, as well as negative studies Rybakowski et al., 1974, Zvolsky et al., 1975, Knorring et al., 1976, Kocsis et al., 1982. There are also several studies of other biological predictors; C973A polymorphism in the inositol polyphosphate 1-phosphatase gene (Steen et al., 1998), lower intracellular pH (Kato et al., 2000a), and white matter hyperintensity detected by magnetic resonance imaging (Kato et al., 2000b). On the contrary, the presence of HLA-A3 antigen was associated with poor response to lithium Del Vecchio et al., 1981, Maj et al., 1984, Maj et al., 1985. However, few of them were replicated.

Electroencephalographic test is one of the least invasive physiological tests routinely used in clinical practice. Since all mood stabilizers other than lithium are anticonvulsants, there may be some relationship between lithium response and electroencephalogram (EEG) finding, especially, epileptiform abnormalities. In pilot studies, with regard to auditory-evoked potentials, steeper slope of the amplitude/stimulus intensity function (N1/N2 component) and N1 latency were detected as potential predictors of positive lithium response in affective psychosis Hegerl et al., 1987, Hegerl et al., 1992. However, the predictive value of routine electroencephalographic test for lithium treatment has not been examined yet.

In this study, the authors examined the possible relationship between EEG finding and lithium response retrospectively.

Section snippets

Subjects

The subjects were 58 patients (36 females and 22 males) who met the inclusion criteria. They consisted of 24 outpatients referred to the University of Tokyo Hospital's bipolar disorder clinic, which was managed by one of the authors, and 34 patients who were hospitalized in the University of Tokyo Hospital over 3 years (January 1998 to December 2000). The inclusion criteria were bipolar disorders of DSM-IV criteria (American Psychiatric Association, 1994). The exclusion criteria were comorbid

Results

Forty-three (73%) of the 59 patients had been treated with lithium. EEG had been examined and recorded in medical charts of 32 (54%) patients. As a result, information both on EEG and lithium response could be obtained from 27 (46%) patients. With regard to these 27 patients, duration of pharmacotherapy in this hospital was 62.8±69.3 months (mean±S.D.).

Only five cases were classified as lithium responders, while the other 22 patients were categorized into nonresponders. Of the 27 patients, 5

Proportion of lithium responder

In this sample, the rate of responder (18.5%, 5/27) was much lower than in previous studies (65.6% of female and 61.0% of male) (Viguera et al., 2000). There are several possible explanations.

First, serum lithium concentration might be lower to get sufficient effect. The range of serum lithium concentration in this study (0.3–1.2 mM) is lower than that with the reported standard dose used for bipolar disorder in North America (0.8–1.5 mM) (Report of the APA Task Force, 1975). However, the

Conclusion

This retrospective study suggests that epileptiform EEG abnormality is worth studying further as a possible predictor of lithium resistance in bipolar disorder.

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