T. Kapitany

Bright light therapy stabilizes the antidepressant effect of partial sleep deprivation.

Partial sleep deprivation (PSD) results in a pronounced decrease of depressive symptoms in the majority of patients with major depressive disorder. Generally this acute antidepressant effect is not stable, relapse usually occurs after one night of recovery sleep. We therefore studied whether light therapy, beginning in the morning after PSD, is able to prevent the relapse after sleep deprivation, using a controlled, balanced, parallel design. All patients received an antidepressant medication, which was kept constant before and during the study period. Fourteen of 20 patients (70%) showed a reduction of at least 40% in the Hamilton Depression Rating Scale (HDRS) in the morning after PSD and were classified as PSD responders. Responders as well as nonresponders were randomly assigned to receive either bright light (BL/3000 lux) or dim light (DL/100 lux) therapy during the following 6 days after PSD. In the responder group BL therapy prevented significantly (p = 0.005) the relapse after the next night of sleep and prolonged significantly (p = 0.011) the antidepressant effects of PSD up to 7 days. In contrast, patients in the DL condition relapsed after the recovery night and showed no further improvement of the depressive syndrome after 1 week of DL therapy. PSD nonresponders did not benefit from light treatment. These findings indicate that BL therapy might be efficacious to prevent relapse after PSD.

Genetic polymorphisms for drug metabolism (CYP2D6) and tardive dyskinesia in schizophrenia.

In the present study, the occurrence of tardive dyskinesia (TD) in chronic schizophrenia patients was investigated in relation to pharmacogenetic polymorphisms. It is known that the metabolism of important neuroleptic drugs is influenced by polymorphisms of the CYP2D6 gene, which encodes the cytochrome P450 enzyme debrisoquine/spartein hydroxylase. Forty-five patients meeting the DSM IV criteria for schizophrenia, chronic course, were recruited. The patients were examined for the mutations CYP2D6*3, CYP2D6*4 and CYP2D6*5. The CYP2D6 genotype distribution in the patient group did not differ from that in healthy Caucasian populations. Tardive dyskinesia was found in 26 patients (57.8%). When comparing patients without CYP2D6 mutations with patients heterozygous for one mutation, we found a higher incidence of TD in the latter (81.3% vs. 46.4%, p = 0.031, multiple regression analysis), which demonstrates a significant influence of the CYP2D6 genotype of the manifestation of TD. As slight differences in the metabolism of drugs in patients heterozygous for CYP2D6 mutations and patients without such mutations are known, we conclude that heterozygous carriers of 2D6 mutated alleles may show an increased susceptibility to developing TD.

The citalopram challenge test in patients with major depression and in healthy controls

Neuroendocrine challenge tests in depressed patients have revealed a blunted hormonal reaction to serotonergic stimuli. In the present study, citalopram was chosen as the serotonergic agent for neuroendocrine stimulation. Compared to earlier challenge agents, citalopram has the advantage of serotonergic selectivity, its application is well tolerated and the possibility of intravenous application reduces pharmacokinetic interference. Sixteen patients suffering from an acute episode of major depression and 16 healthy controls underwent the stimulation procedure with 20 mg of citalopram and placebo. Whereas significant differences in the secretion of prolactin and cortisol between citalopram and placebo challenge were observed in the control group, no differences were found in the group of depressed patients. Comparison of depressed patients and controls showed a significantly blunted prolactin secretion in patients. Differences in cortisol secretion following serotonergic stimulation with citalopram did not become significant. The stimulation procedure was well tolerated in all subjects, although a higher number of side effects was observed in the control group. The amount of side effects did not correlate with the hormone responses. These results are in line with the hypothesis of serotonergic hypofunction in depressed patients. In conclusion, the 20-mg citalopram challenge test is thought to be a promising tool for further investigation of serotonergic function in psychiatric illness.

Color vision deficiencies in the course of acute alcohol withdrawal

Thirty-six male patients with a diagnosis of chronic alcoholism were detoxified and color vision tests were performed on day 4, 11, and 32 of their abstinence on an inpatient basis (Ishihara color plates, Nagel anomaloscope, three color-matching tests according to Farnsworth). Of the 36 patients, 47.2% manifested color vision deficiencies. The frequency of congenital red/green defects (11.1%) and a ratio of 3:1 deutan/protan defects showed no significant difference from the incidence in the normal population. In 36.1%, manifest acquired color vision deficiencies were diagnosed. Within the course of withdrawal, a marked improvement of these disturbances could be proved. The degree of the disturbance seems to correlate with the severity of withdrawal symptoms, but seems to be unrelated to acute toxic effects of alcohol, nicotine, or medication.

Typical neuroleptics vs. atypical antipsychotics in the treatment of acute mania in a natural setting.

The present retrospective chart review documents the treatment practice of in-patients suffering from acute manic or hypomanic episodes, at the Department of General Psychiatry, Medical University of Vienna between 1997 and 2001. The aim of the study was to compare the efficacy of typical neuroleptics and atypical antipsychotics as add-on therapy to mood stabilizers. A total of 119 episodes of consecutively admitted patients with ICD-10-defined acute mania (n=106) or hypomania (n=13) were included in a retrospective analysis. Two subgroups were separated out of the whole patient sample according to the medication used: (a) mood stabilizer+typical neuroleptic (n=27) and (b) mood stabilizer+atypical antipsychotic (n=39). The treatment patterns of both subgroups during the first 14 d of in-patient treatment were evaluated. The therapeutic effect was measured by the Clinical Global Impression Scale (CGI). Both patient groups showed no differences on CGI at admission. Patients treated with atypical antipsychotics showed a significantly greater clinical improvement after 14 d (p<0.005) and on discharge (p<0.05) than patients treated with typical neuroleptics. Furthermore, patients treated with atypical antipsychotics developed significantly less extrapyramidal side-effects (p<0.01) and were significantly treated less often with benzodiazepines (p<0.05) during the first 14 d compared to the group receiving typical neuroleptics. Based on our evaluation and the data available in the literature atypical antipsychotics can be considered as first choice for the treatment of acute mania as add-on therapy to mood stabilizers because of their better efficacy and side-effect profile compared to typical neuroleptics.

Psychogene nicht-epileptische Anfälle

Unter psychogenen, nicht epileptischen Anfallen (PNE Anfalle) versteht man paroxysmale Verhaltensschemata, die epileptischen Anfallen in ihrer klinischen Symptomatik ahnlich sind, denen allerdings keine organische Storung der Hirnfunktion zu Grunde liegt, und die somit auch nicht mit EEG-Veranderungen einhergehen (Lesser 1996). PNE Anfalle sind ein indirekter Ausdruck eines psychischen Konflikts bei zugleich gestorter direkter verbaler und emotionaler Kommunikation, wobei es zu einer Verlagerung des Ausdrucks auf eine korperlich symbolische Ebene kommt. PNE Anfalle werden in der Internationalen Klassifikation psychischer Storungen, ICD-10 (WHO 1991) als „Dissoziative Krampfanfalle“ der Gruppe Dissoziativer Storungen zugeordnet (Scheidt und Flugel 1997). In der amerikanischen Klassifikation DSM-IV werden sie als „Konversionsstorung mit Krampfanfallen“ den somatoformen Storungen zugeteilt (Bowman 1999).

Genotypisierung des Cyp 2D6-Polymorphismus in einer Gruppe chronisch schizophrener Patienten mit therapeutisch ungünstigem Verlauf

Der genetisch bedingte Metabolisierungsdefekt des Cytochrom P450 Isozym Cyp 2D6 wird mit einer Haufigkeit von 3–10% in kaukasischen Populationen autosomal rezessiv vererbt. Phanotypisch wurde diese Storung durch Metabolisierungsbestimmungen mit den Substanzen Spartein bzw. Debrisoquin festgestellt. Ursache fur den Defekt ist das gleichzeitige Vorkommen von Mutationen im verantwortlichen Gen Cyp 2D6 auf beiden homologen Chromosomen 22. Klinisch kommt es bei betroffenen Personen zu stark erhohten Plasmaspiegeln und daraus folgenden Problemen in der Therapie mit entsprechenden Substanzen (z. B. verschiedene Phenothiazine oder Haloperidol).