I. Kurzthaler

Hepatotoxicity of clozapine.

Two hundred thirty-eight patients treated with either haloperidol or clozapine were investigated to shed more light on the incidence and severity of antipsychotic-induced liver enzyme increase. Serum glutamic-pyruvic transaminase (SGPT) increase was most frequently seen in both treatment groups. When analyzing the incidence rates for patients with increased liver enzyme values (serum glutamic-oxaloacetic transaminase, SGPT, gamma-glutamyl transpeptidase) that were higher than twice the upper limit of the normal range, clozapine-treated patients showed an SGPT increase (37.3%) significantly more frequently than patients treated with haloperidol (16.6%). Both patients with higher clozapine plasma levels and male patients were at a higher risk for an SGPT increase. At least 60% of the increase of the different enzymes remitted within the first 13 weeks of treatment. In general, the authors conclude that clozapine-induced liver enzyme elevation seems to be a common and mostly transient phenomenon. (J Clin Psychopharmacol 1997;17:314-317).

Trends in the pharmacological treatment of patients with schizophrenia over a 12 year observation period

In this study we evaluated whether our efforts to promote evidence-based guidelines for the psychopharmacological treatment of patients with schizophrenia have led to measurable changes of treatment practice in our hospital by investigating three primary hypotheses: 1) Polypharmacy has become less common in recent years, 2) Conventional neuroleptics have been replaced by second generation antipsychotics; and 3) Dosing regimes have changed towards lower doses. We have therefore collected data from the clinical records of all in-patients with ICD-9/ICD-10 diagnoses of schizophrenia hospitalized at the Department of Psychiatry of the Medical University Innsbruck in the years 1989, 1995, 1998 and 2001. Data from 1989 to 1998 showed a significant decrease in the use of two or more antipsychotics given simultaneously. Contrary to our hypothesis, there was a significant increase in polypharmacy between 1998 and 2001. The predominant use of second generation antipsychotics became standard in schizophrenia treatment. In this context the decrease of concomitant anticholinergic medication is notable. Doses of conventional antipsychotics like haloperidol as well as doses of risperidone decreased whereas doses of other second generation antipsychotics increased. All in all, the pharmacological management of schizophrenia patients is increasingly in tune with current treatment guidelines.

Risk factors for the development of neuroleptic induced akathisia

Neuroleptic induced akathisia (NIA) is a common and distressing side effect of antipsychotic treatment. Incidence rates are reported to be between 25% and 75%, depending on criteria used for diagnosis. The results of our four week prospective naturalistic study are based on the assessment of 73 inpatients, which were started on antipsychotic medication in one of the inpatient units of the Department of Psychiatry. NIA was rated with the Hillside Akathisia Scale. Assuming that both, objective as well subjective phenomena are necessary for a valid diagnosis of NIA, we calculated an incidence rate of 22.4%. 75% of all NIA cases occurred within the first three days of antipsychotic treatment. When attempting to determine risk factors for the development of NIA, we found a significant influence of dose increase in the first days of treatment.

The safety of clozapine in the treatment of first- and multiple-episode patients with treatment-resistant schizophrenia

The importance of antipsychotics in the treatment of schizophrenia has been documented in numerous clinical trials. In addition to its established superiority over other antipsychotics in treatment-resistant patients, clozapine has been consistently shown to improve psychopathology and other psychosocial outcome variables in patients with schizophrenia. To determine whether the course of the illness has an influence on response and side-effects to clozapine, we directly contrasted first- and multiple-episode patients with schizophrenia, who had histories of failing response to traditional antipsychotics, during the acute treatment phase. Thirty-nine first-episode patients with schizophrenia and 56 patients who had suffered from at least two episodes of this illness were investigated. Severity of illness and clinical improvement were rated by means of the CGI Scale. Vital signs were recorded weekly. Side-effects were regularly assessed with the UKU Side Effect Rating Scale. Compliance was regularly assessed by clinical interviews and plasma level monitoring. By using comparable mean clozapine doses, the number of treatment responders was similar in both groups (first-episode patients, 51.3%; multiple-episode patients, 46.4%). However, we found a negative association between age and response rate. With regard to side-effects, we could not find any significant difference between groups. Altogether, response and side-effects to clozapine treatment do not seem to be determined by the chronicity of the disorder.

[The role of alcohol and/or benzodiazepines in occupational accidents compared to accidents due to other causes].

SummaryAll patients who were admitted within one year to the Department of Traumatology of the Innsbruck University Hospital as a result of an accident were included in this epidemiological study: a total of 1611 patients. 18.9% (n = 304) of these patients were injured as a result of a work-related accident and the remaining 81.2% (n = 1307) were involved in accidents due to other causes. Within the group of patients involved in work-related accidents, alcohol consumption was more frequent in males (13.3%) than in females (1.8%) (p = 0.016) and clearly lower than in patients injured by accidents due to other causes. In work-related accidents we found a correlation between the educational standard of patients and the frequency of alcohol consumption. The mean blood alcohol concentration was lower in patients involved in work-related accidents (0.76 ± 0.58 g/l) than in those involved in other injuries (1.63 g/l ± 0.74 g/l). No correlations were found concerning benzodiazepine use and demographic variables and all measured benzodiazepine plasma levels were within the therapeutic range.ZusammenfassungIn die Untersuchung wurden all jene Patienten, die innerhalb eines Jahres aufgrund ihrer Verletzungen im Rahmen eines Unfalles an der Unfallchirurgischen Ambulanz untersucht und anschließend stationär aufgenommen wurden, eingeschlossen. 304 (18,9 %) Personen verletzten sich im Rahmen eines Arbeitsunfalls, 1307 (81,2 %) Patienten erlitten Verletzungen durch Unfälle anderer Genese. Allen Patienten wurde eine Blutprobe entnommen, um einen eventuellen Alkohol- und/oder Benzodiazepinkonsum nachzuweisen. Zum Unfallzeitpunkt wiesen deutlich mehr männliche (13,3 %) als weibliche Patienten (1,8 %) positive Blutalkoholspiegel auf (p = 0,016). Der größte Anteil von alkoholisierten Patienten (17 %) fand sich in der Gruppe der un- und angelernten Arbeitskräfte, während Akademiker und Facharbeiter sowie Pensionisten eine niedrigere Alkoholisierungshäufigkeit aufwiesen (9,4 %, 6,7 %). Alle drei Gruppen waren bezüglich der gemessenen Blutalkoholkonzentrationen (BAC s) vergleichbar (0,76 ± 0,56 g/l, 0,66 ± 0,62 g/l, 0,83 ± 0,65 g/l). Auch die durchschnittliche Blutalkoholkonzentration (BAC) war bei Patienten mit Arbeitsunfällen deutlich niedriger als in der Vergleichsgruppe. Benzodiazepinkonsum korrelierte mit keiner der untersuchten demographischen Variablen. Blutplasmakonzentrationen bewegten sich im therapeutischen bzw. subtherapeutischen Bereich. Alkoholkonsum zeigte keinen Einfluss auf die Ausprägung der erlittenen Verletzung, bei den Benzodiazepinen hingegen zeigte sich ein Trend in Richtung eines Zusammenhanges zwischen Benzodiazepinkonsum und höherem Verletzungsgrad.

Special gender issues in psychiatry

Abstract: Significant gender differences exist in the course, manifestation and treatment of mental illness. Regardless of specific diagnosis age is one of the key factors in gender differences. Such differences between the sexes exist not only concerning origin and perpetuation of specific psychiatric diseases, they are also available and notable in specific fields of pharmacological and psychotherapeutically treatment. That review should sensitize clinicians for their responsibility to provide individualized, optimally effective, gender-specific care to patients suffering from mental diseases in some special topics. It should be a short overview considering some important gender details illustrated in concern with the epidemiological background, the symptoms and general used psychiatric treatment strategies of some frequent psychiatric diagnoses.

Hepatotoxicity of clozapine

Two hundred thirty-eight patients treated with either haloperidol or clozapine were investigated to shed more light on the incidence and severity of antipsychotic-induced liver enzyme increase. Serum glutamic-pyruvic transaminase (SGPT) increase was most frequently seen in both treatment groups. When analyzing the incidence rates for patients with increased liver enzyme values (serum glutamic-oxaloacetic transaminase, SGPT, gamma-glutamyl transpeptidase) that were higher than twice the upper limit of the normal range, clozapine-treated patients showed an SGPT increase (37.3%) significantly more frequently than patients treated with haloperidol (16.6%). Both patients with higher clozapine plasma levels and male patients were at a higher risk for an SGPT increase. At least 60% of the increase of the different enzymes remitted within the first 13 weeks of treatment. In general, the authors conclude that clozapine-induced liver enzyme elevation seems to be a common and mostly transient phenomenon.