[Endocrine changes within the scope of psychiatric diseases].
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Biomedical subjects
Publications and source records attributed to S Kasper.
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The majority of depressive disorders may be viewed as a recurrent condition with the possibility of a deteriorative effect on the quality of life and productivity. The results of clinical investigations suggest that anti-depressant medication should be continued for a period of 4-6 months after the acute episode has been resolved (continuation therapy). What is more controversial, however, is the view that patients who have fully recovered should continue to receive medication in an attempt to prevent a future episode from taking place (maintenance therapy). Taking into account the results of empirical investigations which have shown that depressive disorders appear to become more severe and potentially refractory with each new episode, it is argued that patients at risk for recurrent episodes should receive a maintenance pharmacotherapy. The present study reviews the rationale and practical guidelines for the long-term treatment of affective disorders.
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We examined the relationship between plasma concentrations of specific acting antidepressants (fluvoxamine/maprotiline) and clinical improvement as well as the impact of the magnitude of the plasma concentration of these antidepressants on side effects. Patients (32 patients with major depression) were treated within a double-blind parallel trial for four weeks and plasma concentrations were obtained before, on days 8 and 28 of the trial. Although there was a fixed-flexible dosage design it was apparent that 16 patients (89%) of the fluvoxamine group and all patients of the maprotiline group received a dosage between 200 and 300 mg/day in the last week of the trial. Plasma concentrations (mean +/- SD micrograms/l) of fluvoxamine were 125 +/- 91 and 142 +/- 108 on days 8 and 28, respectively and the range of fluvoxamine plasma concentrations on day 28 was from 20 to 417 micrograms/l. Plasma concentrations (mean +/- SD micrograms/l) of maprotiline were 146 +/- 62 and 202 +/- 134 on days 8 and 28, respectively and the range of maprotiline plasma concentration on day 28 was from 12 to 428 micrograms/l. There was no linear relationship between plasma concentrations of both antidepressants (fluvoxamine/maprotiline) and oral dosage. Whereas there was no correlation between fluvoxamine concentration and clinical response there was a tendency that higher maprotiline concentrations were associated with a better antidepressive efficacy at the end of the trial. Higher concentrations of fluvoxamine as well as of maprotiline were significantly (P < 0.05) associated with more side effects.
Most depressive disorders can be viewed as recurrent conditions that may reduce quality of life and productivity. Results of controlled clinical trials indicate that patients should receive 4-6 months of continuation therapy after remission of the acute phase of the illness. Patients at risk of recurrent episodes, however, should receive maintenance pharmacotherapy as depressive disorders appear to become more severe and potentially refractory with each new episode. This paper reviews a rationale and practical guidelines for long-term treatment of depressive disorders.
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The striatal dopamine-D2-receptor uptake of 123I-IBZM in 32 patients (18 without and 14 under therapy with typical neuroleptics) was measured semiquantitatively using different ROI techniques. The aim of the study was to evaluate the influence of these techniques on the different ratios (striatum/cortex) found by various examiners. Using the same SPECT system no major differences were found between rectangular and manually drawn ROIs of the same size. All ROI techniques could differentiate between patients with and without therapy on a highly significant level. Therefore, the resulting ratio is mainly dependent on the spatial resolution of the camera system and only to a relatively minor extent on the ROI technique. Ratios obtained by different observers are not comparable quantitatively.
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Recurrent brief depression (RBD) and seasonal affective disorder (SAD) have been both recently described as subgroups of major depression (DSM-III-R). We have established a relationship between these two syndromes in a cohort of 42 outpatients who presented themselves to a clinic for seasonal affective disorder at the Psychiatric Department of the University of Bonn, FRG. Our preliminary data indicate that 31% of the patients who were diagnosed as suffering from either SAD or its subsyndromal form (S-SAD) can also be categorized as RBD (RBD-seasonal) in a 1-year observation period. During the time span of 1 year RBD-seasonal patients had a mean number of 20 (SD 9) episodes compared with 6 (SD 5) episodes (P less than 0.001) in the group of seasonal patients without BRD. These episodes were accentuated in fall/winter and outnumbered those in spring/summer significantly (P less than 0.001). The mean duration of each episode was 4.6 (SD 2.6) days in the RBD-seasonal group and 21.8 (SD 29) in the non-RBD-seasonal group. Patients with RBD-seasonal experienced seasonal changes as more of a problem and reported a lower percentage of first-degree relatives with a history of depression than the non-RBD-seasonal group.
The neuroleptic effect and tolerability of roxindole (EMD 49,980), an agonist of the dopamine-D2 autoreceptor, was studied during a 4 week treatment period in 7 patients with paranoid-hallucinatory schizophrenia (ICD-9: 295.3). In patients with a daily dosage of up to 4.5 mg/day, there was no improvement as measured with the total score of the BPRS scale. In contrast, patients with a daily dosage of up to 30 mg/day showed a slight improvement, especially in items associated with negative symptoms. In 3 patients there were slight adverse events (dizziness, hypersalivation, hypotonia, nausea/vomiting, miction disturbance) which were probably connected with the intake of roxindole.
The early and chronic effects of 17 beta-estradiol on vasoactive intestinal peptide (VIP) gene expression in rats were examined. Total RNA of four VIP-producing tissues were subjected to Northern blot analysis 15 and 30 min, and 1, 3, 6, and 24 h after a single injection of 17 beta-estradiol (100 micrograms/kg ip). Pituitary, hypothalamus, brain, and ileum VIP messenger RNA (mRNA) levels rose in a time-dependent manner after estrogen treatment. In the pituitary, the increase was maximal at 30-60 min, whereas in the hypothalamus, the increase reached significance only at 3 h but then persisted until at least 24 h. In the brain, a transient increase in VIP mRNA was observed at 30 min, whereas VIP mRNA levels in the ileum responded in a biphasic pattern; the initial early increase was followed by a second elevation occurring at 6 h. A smaller 1-kilobase VIP-related transcript particularly abundant in the pituitary was regulated in parallel with the 1.7-kilobase mature VIP mRNA species. Continuous estrogen stimulation for 7 weeks dramatically increased both mRNA species in the pituitary but did not affect VIP mRNA levels in the other tissues. These data suggest that the regulation of VIP gene expression by transient increases in estrogen levels is rapid and that the pattern of induction is tissue specific.
Selective serotonin reuptake inhibitors (SSRIs) are a recently developed class of drugs with significantly greater antidepressant efficacy than placebo. Generally, in double-blind comparative trials, all SSRIs demonstrated antidepressant efficacy similar to that of the 'standard' tricyclic antidepressants amitriptyline and imipramine; a meta-analysis of controlled trials found the efficacy of the SSRIs to be equivalent to that of the 2 tricyclics. Nevertheless, because of small patient numbers included in most studies that compare SSRIs with other antidepressants, no definitive statements about relative efficacy can be made. In these studies it is simply possible to state that no statistically significant differences were identified between SSRIs and the comparative antidepressants. Importantly, differences in clinical characteristics exist between the SSRIs-differences in elimination half-life (t1/2 beta) between fluoxetine and/or its metabolite (total t1/2 beta = 330 hours) and other SSRIs (t1/2 beta range = 15 to 30 hours), for example. This has implications in terms of potential drug interactions and must be considered when patients have to be switched to treatment with monoamine oxidase inhibitors. Studies with fluvoxamine have been conducted in both in- and outpatients, whereas trials with other SSRIs have been confined largely to outpatient populations. Fluvoxamine has been associated with a high incidence of nausea (37%), although this may have resulted from high initial dosages (rather than upward dose titration protocols) used in early trials. Of further interest, fluoxetine doses of 20mg may be sufficient to produce a satisfactory antidepressant response, and this SSRI may be particularly useful in patients with chronic retarded depression. More clinical data are required before the efficacy of sertraline and citalopram relative to standard antidepressants can be clearly defined. Preliminary data indicate that SSRIs are effective in the treatment of panic disorder, obsessive-compulsive disorder (OCD), eating (e.g. anorexia and bulimia) and personality disorders (e.g. anger, impulsiveness) and substance abuse (e.g. alcoholism); early results with fluvoxamine in the treatment of panic disorder and OCD, and with fluoxetine in the treatment of bulimia, personality disorders and alcohol abuse, have been encouraging. SSRIs have a more favourable tolerability profile than tricyclic antidepressants and, unlike the tricyclics, are not associated with anticholinergic adverse effects, sedation, cardiotoxicity or weight gain. SSRIs are associated with a relatively high incidence of nausea, particularly if high doses are used at the start of treatment. However, the incidence of nausea appears to decrease as treatment is continued.(ABSTRACT TRUNCATED AT 400 WORDS)
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We report the case of a 40-year-old woman with a seasonal form of obsessive compulsive disorder (OCD) which was usually accompanied by obsessions and occurred only in autumn or winter. Frequently, the OCD symptomatology was accompanied by depression. After a 12-day treatment with full spectrum bright light (3000 lux; 2 hours a day between 9 and 11 am) without changing the long-term antidepressive medication (125 mg amitriptyline/day) there was a complete remission of OCD symptomatology, with no relapse during the next months.
Disturbances of the sleep-wake cycle are frequently seen in affective illness and are exhibited in other psychiatric illness as well. In addition to being a useful research probe, manipulations of the sleep-wake cycle such as sleep deprivation (SD) and phase advance can cause depression to remit and thus can be used as alternative or as adjunctive to pharmacologic treatment. The antidepressant response to SD occurs whether antidepressant drugs are administered or not. However, there is some evidence that the concomitant use of antidepressants may prevent the relapses that occur after recovery sleep. Data from clinical investigations also indicate that disrupted sleep can trigger and intensify mania. Rapid cycling bipolar patients may be especially vulnerable to mania/hypomania after disrupted sleep or SD. Characteristic changes in body temperature have been recorded in sleep deprivation as well as in other antidepressant treatment modalities. Thermoregulatory physiology may therefore provide a framework for understanding the effects of sleep-wake manipulations in affective illness.
The Seasonal Pattern Assessment Questionnaire (SPAQ) was used to evaluate retrospectively self-reported seasonal changes in mood and behavior (seasonality) of two normal and six clinical populations: patients with winter-seasonal affective disorder (SAD), summer-SAD, eating disorders, bipolar affective disorder, major depressive disorder and subsyndromal winter-SAD. The SPAQ successfully discriminated between groups expected to have high seasonality scores, such as winter-SAD, summer-SAD and subsyndromal winter-SAD, and normal controls. Bipolars and major depressives had normal seasonality scores. Patients with eating disorders had unexpectedly high scores. There was a general tendency for all groups to eat and sleep more and to gain weight in the winter. The implications of these findings are discussed.
Epidemiological studies and studies of clinical populations suggest that there are primarily two opposite patterns of seasonally recurring depressions: summer depression and winter depression. In addition, there is preliminary evidence that the two seasonal types of depression may have opposite types of vegetative symptoms. In the present study, we prospectively monitored symptoms of depression in 30 patients with recurrent summer depression and 30 sex-matched patients with recurrent winter depression and compared the symptom profiles of the two groups. Consistent with predictions based on the earlier reports, we found that winter depressives were more likely to have atypical vegetative symptoms, with increased appetite, carbohydrate craving, weight gain and hypersomnia, and that summer depressives were more likely to have endogenous vegetative symptoms, with decreased appetite and insomnia. A cluster analysis performed on the patients' symptom profiles without reference to season of occurrence of their episodes separated 78% of the summer depressives and winter depressives from each other on the basis of their symptoms (chi 2 = 19.29, P less than 0.001).
Immunological parameters were studied before and after phototherapy, with bright and dim light, in 38 individuals with a range of retrospectively reported seasonal changes in mood and behavior. There was a significant negative correlation between the degree of mood and behavioral difficulties in fall and winter (seasonality) and the total number of circulating natural killer cells. Changes in the numbers of circulating helper T cells correlated significantly with changes in mood following phototherapy. Moreover, mitogen-induced lymphocyte blastogenesis increased significantly after phototherapy, but there was no significant difference between the bright and dim light treatments. The results suggest that cellular immune function is associated with both seasonality and response to phototherapy.