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Background: The objective of this study was to survey the consistency of the clinical diagnostics and the psychopharmacological treatment of schizophrenia and delusional disorders suffered by older persons. A further aspect was to record significant clinical differences and also similarities between the patient groups in care, matching with the criteria of ICD 10 for schizophrenia (F20), persistent delusional disorders (F22) and schizoaffective disorder (F25)., Methods: Retrospective analysis with reference to the manually and electronically recorded patient medical records of an acute case care ward for geriatric psychiatry and psychotherapy., Results: During the assessment period 210 patients over the age of 65 years were included consecutively in the study (F20 - 64 patients, F22 - 78 patients, F25 - 64 patients, 4 patients died). Ignoring the fact that many of the patients were admitted without a diagnosis, the diagnostic classification of the referring doctor, above all those made by general practitioners, proved to be very consistent for the groups F20 and F25. In the group F22 diagnoses, however, up to almost one half of the referred patients were incorrectly admitted with an F20 diagnosis. The patients included in group F22 formed a heterogeneous group, or a melting pot for various sub-groups, with the common shared characteristic of being comprised of persons suffering from a delusional disorder. These differed from the other two groups in the following attributes: the patients were either older or very old persons, they were mostly receiving inpatient treatment for the first time and subsequently had fewer re-admissions. They also suffered more frequently from both psychiatric and somatic comorbidities; furthermore they included elderly people who had suffered from learning deficiencies or borderline intellectual deficiencies throughout their earlier lives. The patients in groups F20 and F25 differed primarily only in terms of their psychiatric medication, with significantly more mood stabilizer prescribed in the F25 group. Patients in all three groups frequently received tranquilisers during the day and sedatives in the evening, atypical antipsychotics were prescribed in the great majority of cases., Conclusion: The referral diagnoses of patients suffering from many years of schizophrenic type illnesses were largely in compliance with the diagnostic criteria, a much more difficult issue for the referring doctors was the allocation of patients with a first occurrence of delusional symptoms. Those patients who were allocated to the diagnostic group schizophrenia differed significantly from patients from the group with delusional disorders.

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.

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.

Although the selection of patients is known to be a powerful factor affecting the results of clinical trials, little is known about recruitment issues. Many patients with schizophrenia who are screened for a clinical trial of an investigational antipsychotic are ultimately not included in the study. Therefore, the question arises of whether the results obtained by studying a selected group of patients are really representative of the general population of patients with schizophrenia. The authors studied possible reasons for selective sampling in 200 patients who were consecutively admitted to inpatient units of Innsbruck's Department of Psychiatry with a diagnosis of schizophreniform or schizophrenic disorder over a time period of 33 months. Apart from demographic data and a psychopathologic rating (using the Brief Psychiatric Rating Scale), the authors recorded whether or not a patient was included in a phase III study and whether or not those were not included would have theoretically been eligible for such a study. Twenty-seven patients were finally recruited for a clinical trial. These patients were younger, on average, had a more recent onset of illness, and had experienced fewer psychotic episodes in the past. A history of noncompliance with previous treatment and the refusal of consent were the most common reasons for not including theoretically eligible patients in a clinical trial.

Objective: The aim of this study was to evaluate the frequency and course of sexual disturbances associated with clozapine and haloperidol and their potential influence on compliance with medication regimens in patients with schizophrenia., Method: The authors prospectively investigated 153 patients with schizophrenia who received clozapine (N = 100) or haloperidol (N = 53) in a drug monitoring program., Results: The frequency of sexual disturbances was lower in female patients than in male patients. There was no statistically significant difference between the patients taking haloperidol and those taking clozapine in the frequency of these disturbances. Clozapine plasma levels had a significant effect on diminished sexual desire and functional disturbances in male patients. Functional disturbances and diminished sexual desire did not have any influence on compliance in patients taking either haloperidol or clozapine., Conclusions: There was no statistically significant difference between haloperidol and clozapine in regard to their propensity to induce sexual side effects.

Background: Previous studies of clozapine pharmacokinetics have shown a wide intra- and inter-individual variability of plasma levels in patients on stable clozapine doses. We investigated dose-plasma level relationships and intra-individual variability of plasma levels during maintenance treatment with clozapine., Method: Forty-one patients on clozapine were followed for 26 weeks with repeated plasma level measurements and assessments of co-medication and clinical symptoms. In a second step, 15 patients on stable clozapine doses between treatment Weeks 12 and 52 were followed in the same way. Coefficient of variation was used as a parameter of plasma level deviation., Results: Dose-plasma level correlations stayed significant from Week 6 to Week 26 (n = 41). The group of patients followed up to Week 52 showed a mean intra-individual coefficient of variation of 52.8% (s.d. = 20.6), and remained stable psychopathologically., Conclusions: Even though clozapine plasma levels may show a significant degree of variation, this is not necessarily reflected in a change in psychopathology.

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.

The atypical antipsychotic clozapine carries a high risk of inducing agranulocytosis. We attempted to investigate whether eosinophilia during clozapine treatment has predictive value for subsequent neutropenia/agranulocytosis. One hundred and seventy-seven patients were studied in a prospective naturalistic design using haloperidol as the reference compound. Clozapine was found to differ from haloperidol in respect to their influence on neutrophil granulocytes. In the clozapine group patients with eosinophilia showed a decrease in neutrophil count (less than 2000/mm3 neutrophil granulocytes) significantly more often than patients without eosinophilia.

Patients were investigated to gain more insight into the incidence and time course of clozapine induced weight gain (n = 81) and to compare weight gain in patients treated with clozapine (n = 31) with that of patients treated with standard antipsychotics (haloperidol, n = 11). 35.7% of the patients treated with clozapine gained weight according to our definition. If patients gained weight on clozapine this side effect was apparent within the first 12 weeks of treatment. Deviation from normal body weight at the beginning of treatment showed a significant influence on weight gain. Sex, severity of illness, comedication, mean clozapine dose and degree of improvement did not show an influence on this side effect. Weight increase was significantly higher in patients treated with clozapine than in patients treated with haloperidol.

In addition to other factors such as type and duration of treatment, patient- and illness-related variables and other psychosocial features, side effects are known to exert a significant influence on the compliance with antipsychotic treatment. This has been demonstrated for extrapyramidal motor side effects and akathisia, sedation, weight gain and sexual dysfunctions. Other adverse events interfering with the patients' social roles also interfere with the patients' willingness to comply with treatment. It is important to acknowledge this not only in the acute treatment of schizophrenia but especially during maintenance and prophylactic treatment. Compliance can be considerably improved by a) adequately informing the patient about the risks and nature of side effects and b) by recognizing and treating side effects, since prevention of adverse events is not easily achieved. An underestimation of the influence of side effects on compliance will often lead to treatment failures that are erroneously attributed to treatment resistance.

We obtained pharmaco-epidemiologic data regarding the antipsychotic maintenance treatment (AMT) of schizophrenia patients through a postal survey sent to all Austrian psychiatrists and neurologists. Drug therapy was considered the most important therapeutic approach in the long-term management of schizophrenia. However, the majority of the respondents clearly were not satisfied with the current status of scientific knowledge about dosage and duration of AMT. Single-drug treatment with antipsychotics was preferred by the respondents; oral and depot neuroleptics were used with equal frequency. Haloperidol was the oral drug most frequently mentioned as first choice (44% of the respondents), followed by clozapine (14.1%) and thioridazine (9.2%). The proposed mean daily doses showed striking variations among respondents. The proposed mean length of maintenance treatment in first-episode patients was 7.3 months; in multi-episode patients, it was 20.1 months. The results show considerable variation in physicians' attitudes toward AMT.