B. Müller-Oerlinghausen

Lithium versus carbamazepine in the maintenance treatment of bipolar disorders - a randomised study

In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in 144 patients with bipolar disorder (74 vs. 70 patients; observation period: 2.5 years; lithium serum level: 0.63 +/- 0.12 mmol/l, carbamazepine dose: 621 +/- 186 mg/day). Hospitalisations, recurrences, need of psychotropic comedication and adverse effects prompting discontinuation were defined as treatment failures. Survival analyses regarding hospitalisations and recurrences showed no statistically significant differences between both drugs. Results were distinctly in favour of lithium, considering recurrences combined with comedication (P = 0.041) and/or adverse effects (P = 0.007). Whereas adverse effects prompting discontinuation were more frequent under carbamazepine (9 vs. 4, ns), lithium patients reported more often slight/moderate side effects (61% vs. 21% after 2.5 years; P = 0.0006). In completers, recurrences occurred in 28% (lithium) vs. 47% (carbamazepine) of the patients (P = 0.06). Lithium seems to be superior to carbamazepine in maintenance treatment of bipolar disorder, in particular when applying broader outcome criteria including psychotropic comedication and severe side effects.

The effect of long-term lithium treatment on the mortality of patients with manic-depressive and schizoaffective illness*

Clinical research centers in Aarhus, Berlin, Hamilton and Vienna collected mortality data for 827 manic‐depressive and schizoaffective patients given lithium treatment for more than 6 months. The average duration of the treatment was 81 months and the total time on lithium 5600 patient‐years. For each patient, the mortality risk was calculated by entering the appropriate national life tables for the general population. The number of observed deaths was 44; the number of expected deaths was 49.7. The standardized mortality ratio, 0.89, did not differ significantly from 1.0. The mortality of manic‐depressive patients is 2–3 times that of the general population. Our data show that the mortality of manic‐depressive and schizoaffective patients given long‐term lithium treatment does not differ significantly from that of the general population.

Mortality during initial and during later lithium treatment : a collaborative study by the International Group for the Study of lithium-treated patients

We have previously shown that the mortality of patients with recurrent affective disorders in long‐term lithium treatment is not higher than that of the general population. In the present study on 471 patients from Denmark and Germany, we examined mortality during the initial year of lithium treatment and during later lithium treatment. During initial lithium treatment, the total mortality was twice as high as in the general population (difference not significant) and the mortality due to suicide 16 times higher. During later lithium treatment, the mortality rates did not differ from those in the general population. Our results indicate that patients with frequent, often severe recurrences, those chosen for prophylactic lithium treatment, are at risk of high mortality, which then diminishes as the prophylactic action of the treatment takes effect.

Changes in learning, memory, and mood during lithium treatment. Approach to a research strategy.

In a double‐blind study the effects of a 14‐day lithium medication (dosage: 24 mval/day to 36 mval/day) were investigated. The subjects were 24 healthy male volunteers. The effect of lithium on their mood, ability to learn nouns, and memory of the words learnt was measured after 2 hours and 14 days. In spite of a relatively low mean plasma lithium level on the 14th day (0.54 ± 0.15 mmol/l), the lithium volunteers assessed themselves after 2 weeks of treatment as significantly less relaxed, less active, less socially involved, more bored, and more tired than the placebo group. As to learning, the lithium group showed only a slight impairment of performance compared with the placebo groups. As to memory, there was a significant difference in free recall over 2 weeks: the lithium group remembered fewer words than the placebo group. Additional motivation of free recall over 2 hours was ineffective. It is discussed whether lithium changes spontaneous initial action and thereby the will to act. This could be interpreted as a change in the production of the characteristics of experience* and behaviour.

PREDICTORS OF RESPONSE TO LITHIUM AUGMENTATION IN TRICYCLIC ANTIDEPRESSANT-RESISTANT DEPRESSION

BACKGROUND The efficacy of lithium augmentation in therapy-resistant depression has been shown in a series of well-designed, placebo-controlled studies. However, little is known about the predictors of a good response to this treatment strategy. METHODS We retrospectively examined the predictive value of 20 demographic, clinical, biochemical and endocrinological variables using a two-step logistic regression. Seventy-one in-patients with depression refractory to tricyclic antidepressants had received lithium augmentation as part of a standardised treatment protocol. RESULTS Within 4 weeks 37 patients (52%) responded to lithium augmentation. Five variables with predictive value were found. Responders were more severely depressed according to the Bech-Rafaelsen Melancholia Scale. The duration of their index episode was shorter. Triiodothyronine serum levels were lower and neuroleptic co-medication and co-diagnosis of personality disorder were less frequent. LIMITATIONS This was an open, retrospective study. CONCLUSIONS Severity of depression is a predictor of response to lithium augmentation. This result conflicts with recent studies but is similar to results found in studies of other pharmacological antidepressant strategies.

Sensation Seeking and Auditory Evoked Potentials

The relationship between auditory evoked potentials (AEP) and the German version of Zuckermans Sensation Seeking Scale was examined. The slope of the amplitude/stimulus intensity function (N1/P2 component) and the N1 latency were particularly studied, as these variables have been found to be potential predictors of the response to lithium prophylaxis. Thirty-three healthy subjects participated in two testing series on the first day and in a third run 3 weeks later. Binaural clicks at four intensity levels (58, 68, 78, 88 dB HL, ISI 2.1 sec) were presented in randomized order by headphone. Eighty responses were averaged at each intensity level. The pattern of correlation between the German version of the Sensation Seeking Scale and a personality inventory (FPI) supports the validity of the Sensation Seeking Scale. Only a tendency toward steeper slopes of the amplitude/stimulus intensity function (ASF) in high sensation seekers was observed in the first run. However, there was a significant interaction of sensation seeking and the test run. Only high sensation seekers showed an influence of retesting on the slope of the ASF, leading to a decrease of the slope in the second, compared with the first run. This might correspond to the psychological pattern of sensation seeking, which is characterized by a permanent need for new and exciting situations and, at the same time, by a rapid loss of interest in these situations. With regard to the N1 latency, a significant interaction of sensation seeking and lead was found. Low sensation seekers showed longer N1 latencies over the right than over the left hemisphere, a finding that accords with some psychophysiological theories on the relation between asymmetric hemispherical activation and certain psychological constructs. Our results support the view that sensation seeking is a personality feature that is closely related to certain physiological variables.

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.

Blood serotonin, serum melatonin and light therapy in healthy subjects and in patients with nonseasonal depression

The 24‐h rhythms of blood serotonin and serum melatonin were determined in 39 unmediated inpatients with nonseasonal affective disorder and in 14 healthy men and women after 7 days of morning bright‐light (2500 lx) or dim‐light (50 lx) treatment. Bright‐light treatment led to a more than 50% decrease in the Hamilton Rating Scale for Depression (HRSD) score in 4/19 patients and dim light in 1/17 patients. After light treatment the mesor (the daily mean estimated by cosinor analysis) of patients’ and subjects’ melatonin levels did not change significantly, nor was there a correlation between phase change and decrease in HRSD score. We observed after bright‐ and dim‐light treatment a consistent increase in blood serotonin in patients and healthy subjects, which differed significantly between healthy subjects and patients. These findings suggest the involvement of serotonergic mechanisms following light therapy.

Peripheral serotonergic markers in acutely suicidal patients. 1. Comparison of serotonergic platelet measures between suicidal individuals, nonsuicidal patients with major depression and healthy subjects

SummaryBackground. A robust association between “suicidality” and deficits of the serotoninergic neurotransmission has been claimed in the past. However, many studies having investigated the relationship between suicidality and peripheral indicators of serotoninergic neurotransmission suffer from considering only one or a very small number of potentially useful serotoninergic parameters, whereas a synoptic multidimensional approach appears to be more appropriate. Furthermore, the psychiatric context within which suicidal behaviour occurs should be considered when interpreting biochemical findings of patients with suicidal ideation and suicide attempts. Methods. In the present study 5 peripheral serotonergic markers, (platelet 5HT concentration, 5HT uptake activity, 5HT2A receptor binding characteristics, MAO-B activity and tryptophan concentration in plasma) were assessed simultaneously. Of the 60 acutely suicidal inpatients (ICD-10: F43.xx, n = 52; F31/32/33, n = 8), 45 were suicide attempters. Data of 28 nonsuicidal patients with major depression (F31, n = 4; F32, n = 14; F33, n = 10) and 123 healthy volunteers represented the control groups. Results. Mean platelet 5HT concentration was significantly lower in suicidal inpatients when compared to nonsuicidal depressed patients, but did not differ from the figure in healthy subjects. Nonsuicidal depressed patients showed significantly higher mean platelet-5HT concentration than healthy controls.Mean Vmax of 5HT uptake in washed platelets, but not in platelet-rich plasma, was significantly higher in suicidal patients than in healthy controls, not, however, when compared to nonsuicidal depressed patients.Mean KD for the platelet 5HT2A receptor and MAO-B activity were significantly lower in suicidal patients as compared to nonsuicidal depressed patients and healthy controls.The observed differences in peripheral serotonergic markers between groups are partially due to a significant gender effect. A lower MAO-B activity was observed only in suicidal females, while the higher Vmax of 5HT uptake in washed platelets of suicidal patients was due to suicidal males. Conclusions. In view of conflicting observations made by other authors and the present findings on suicidal patients with adjustment disorder it remains doubtful whether and if so to which extent platelet studies can provide valid information on serotonergic mechanisms related to suicidal behaviour.

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.