Adolf Pietzcker

First vs multiple episode schizophrenia: Two-year outcome of intermittent and maintenance medication strategies

Results of studies on intermittent neuroleptic treatment strategies in first episode (FE) schizophrenia have not been published. Aims of the present study were to elucidate the comparative efficacy of prodrome-based neuroleptic intervention in first vs multiple episode (ME) schizophrenia. As to the methods, three randomly assigned open neuroleptic treatment strategies were compared over 2 years in 363 schizophrenic outpatients (115 FE, 248 ME; ICD-9, RDC): maintenance medication vs two intermittent medication strategies (prodrome-based intervention and crisis intervention). Concerning relapse prevention, the results demonstrate that ME patients seemed to profit most from maintenance medication compared to both intermittent treatments, whereas FE patients did equally well under maintenance medication and prodrome-based intervention treatment. Psychopathology, social adjustment, subjective well-being, and side-effects after two years did not differ significantly between the FE and ME patients irrespective of treatment strategy. Concerning treatment adherence, FE patients complied better with prodrome-based intervention than with maintenance medication. Cumulative neuroleptic dosage was lowest in FE patients under intermittent treatment. In conclusion, maintenance medication is the best strategy for relapse prevention in ME patients. In FE patients, prodrome-based intermittent intervention seems to be equivalent or even better with respect to compliance and dosage applied.

Intermittent versus maintenance neuroleptic long-term treatment in Schizophrenia—2-year results of a German multicenter study

Abstract The paper presents the 2-year results of a multicenter study on the comparative efficacy of different neuroleptic long-term treatment strategies in 364 schizophrenic outpatients carried out by the German Neuroleptic Treatment Study (ANI) Group. Three randomly assigned open neuroleptic treatments were compared: standard prophylactic maintenance medication, and two types of intermittent treatment (early intervention and neuroleptic crisis intervention). Although relapserates were significantly lower under early intervention (49%) than under crisis intervention (63%), those under maintenance treatment were by far the lowest (23%). Dropout and rehospitalization rates under both intermittent treatment strategies were also significantly less favorable than under maintenance treatment, whereas psychopathology, social adjustment, subjective wellbeing, and side-effects were not significantly different between treatment strategies. Cumulative neuroleptic dosage was significantly lower under intermittent treatment, even when inpatient treatment in a case of rehospitalization was considered. In conclusion, prophylactic maintenance medication turns out again to be the best treatment for most of the patients.

Skalenbildung im AMDP-System

The psychopathological and somatic symptoms documented by the AMDP-system on the admission of 1654 patients to the Psychiatric Clinics of the Universities in München und 659 patients in Berlin were factor analyzed. Eight factors could be extracted which describe the psychopathology on eight syndrome-scales. These factors could be cross-validated by factor analyses on random samples. In correspondence with the factors of the AMP-system the following syndromes were found: paranoid-hallucinatory, depressive, psycho-organic, manic, hostility, autonomic, apathy, obsessive-compulsive. For each of the 70 items which were associated with a factor we computed the percentage occurrence and item-scale-intercorrelations, for each of the eight syndrome-scales reliability-coefficients, intercorrelations and T-transformations. For further data-reduction second-order-factors were also computed.SummaryThe psychopathological and somatic symptoms documented by the AMDP-system on the admission of 1654 patients to the Psychiatric Clinics of the Universities in München und 659 patients in Berlin were factor analyzed. Eight factors could be extracted which describe the psychopathology on eight syndrome-scales. These factors could be cross-validated by factor analyses on random samples. In correspondence with the factors of the AMP-system the following syndromes were found: paranoid-hallucinatory, depressive, psycho-organic, manic, hostility, autonomic, apathy, obsessivecompulsive. For each of the 70 items which were associated with a factor we computed the percentage occurrence and item-scale-intercorrelations, for each of the eight syndrome-scales reliability-coefficients, intercorrelations and T-transformations. For further data-reduction second-order-factors were also computed.ZusammenfassungAnhand der Aufnahmebefunde von 1654 Patienten der Münchener und 659 Patienten der Berliner Psychiatrischen Universitätsklinik wurden Faktorenanalysen über die psychischen und somatischen Merkmale des AMDP-Systems gerechnet. Es ließen sich Faktoren extrahieren, die die Psychopathologie auf 8 Syndromskalen beschreiben. Diese Faktoren konnten durch Kreuzvalidierungen auch an Zufallshälften der Stichproben bestätigt werden. In Übereinstimmung mit den Ergebnissen im AMP-System konnten ein paranoid-halluzinatorisches, ein depressives, ein psychoorganisches, ein manisches, ein Hostalitäts-, ein vegetatives, ein apathisches und ein Zwangssyndrom gefunden werden. Für die 70 den Faktoren zugeordneten Items liegen Schwierigkeits- und Trennschärfenindices vor, für die 8 Syndromskalen Reliabilitäten und T-Transformationen sowie Interkorrelationen. Um eine noch weitere Datenreduktion zu ermöglichen, wurden außerdem Faktoren zweiter Ordnung bzw. übergeordnete Syndrome gebildet.

The hypothalamic–pituitary–thyroid axis in patients with schizophrenia

Serum concentrations of thyroxine (T(4)), triiodothyronine (T(3)), reverse triiodothyronine (rT(3)) and thyrotropine (TSH) were measured in 31 acutely ill in-patients with schizophrenia before and after four weeks of treatment with the phenothiazine derivative perazine. The serum levels of all the above hormones were also determined in 19 schizophrenic patients in remission who were receiving no medication, 20 schizophrenic patients in remission taking neuroleptic drugs, and 24 patients with residual-type schizophrenia. The serum levels of T(4) of acutely ill schizophrenic patients were elevated, while those of T(3), rT(3) and TSH were normal. Their T(4) levels showed a positive correlation with the severity of illness and the degree of clinical response to neuroleptic treatment. There was a significant fall in serum concentrations of T(4) and rT(3) during four weeks of drug treatment and the decrease was significantly correlated to clinical response. No abnormalities in the serum concentrations of any of the hormones measured were found in schizophrenic patients in remission or in residual-type schizophrenia. In conclusion, our results indicate that the elevated serum levels of T(4) may be specific for acutely ill schizophrenic patients and that neuroleptic medication may affect thyroid hormone metabolism, this interaction being involved in the mechanism of action of these drugs.

Depressive syndromes in schizophrenic patients under neuroleptic therapy

SummarySchizophrenic outpatients (=364) were assigned at random to three different treatment strategies: (1) continuous medication with neuroleptic drugs, (2) intermittent medication with crisis intervention and (3) intermittent medication with early intervention. Depressive syndromes were rated according to three different scales for depressive syndromes (Brief Psychiatric Rating Scale anxious depression factor, Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie/depression, and the self-rating Paranoid Depression Scale) after 1 and 2 years of treatment. No differences in depression scores were found between the three treatment strategies. Comparisons between patients treated with neuroleptic drugs at the time and patients without neuroleptics revealed significantly higher depression scores in the neuroleptics group in most comparisons. No differences were found between patients treated with low versus high potency neuroleptics and between oral versus depot neuroleptics. However, depression correlated with extrapyramidal symptoms.

Die Bildung von Syndromen im AMP-System

SummaryThe symptoms of 2269 psychiatric patients on admission, documented by the AMP (PAS) system, were factoranalyzed to build syndromes of psychopathology. The nine syndromes could be cross-validated. We believe a useful description of the findings on admission can be made by the following syndromes: paranoid-hallucinatory, manic, psycho-organic, depressive, apathetic, hostile, stuporous, somatic, compulsive. The correlation with other syndromes based on AMP by other scientists is substantial. For each item we computed the percentage of occurrence and the item-scale correlation, and for the syndrome-scales reliability, intercorrelations and T-transformations. We calculated the mean profiles for some diagnostic groups to test some aspects of the validity of the syndromes. It was demonstrated that a differentiation is possible.ZusammenfassungÜber die psychopathologischen Aufnahmebefunde von 2269 psychiatrischen Patienten, die mit Hilfe des AMP-Systems dokumentiert waren, wurden Faktorenanalysen gerechnet mit dem Ziel, Syndrome zu bilden. Die neun Syndrome ließen sich durch Kreuzvalidierungen reproduzieren. Es kann davon ausgegangen werden, daß das paranoid-halluzinatorische, das manische, das psychoorganische, das depressive, das apathische, das Hostilitäts-, das stuporöse, das vegetative und das Zwangssyndrom eine brauchbare Beschreibung des Aufnahmebefundes darstellen. Es ließ sich eine gute Übereinstimmung mit den Syndromberechnungen im AMP-System durch andere Autoren finden.Für die einzelnen Items liegen Schwierigkeits- und Trennschärfenindices vor, für die Syndromskalen Reliabilitäten, Interkorrelationen und T-Transformationen. Erste Ansätze zur Überprüfung der Validität wurden vorgenommen durch die Berechnung von Durchschnittsprofilen einiger klinischer Gruppen. Dabei konnte gezeigt werden, daß eine Differenzierung möglich ist.The symptoms of 2269 psychiatric patients on admission, documented by the AMP (PAS) system, were factor-analysed to build syndromes of psychopathology. The nine syndromes could be cross-validated. We believe a useful description of the findings on admission can be made by the following syndromes: paranoid-hallucinatory, manic, psycho-organic, depressive, apathetic, hostile, stuporous, somatic, compulsive. The correlation with other syndromes based on AMP by other scientists is substantial. For each item we computed the percentage of occurrence and the item-scale correlation, and for the syndrome-scales reliability, intercorrelations and T-transformations. We calculated the mean profiles for some diagnostic groups to test some aspects of the validity of the syndromes. It was demonstrated that a differentiation is possible.

Prodromal States in Schizophrenia

The vulnerability-stress-coping (VSC) model is the most influential heuristic concept in understanding the course of schizophrenia, whose prodromal status still offers unsolved conceptual and methodological issues. Improved knowledge about the prodromal phase would provide a better understanding of the developing psychopathology and psychophysiology of schizophrenia and could also be of predictive value to attune therapeutic actions to the course of the illness more precisely. To shed more light on the characteristics of prodromal states, data from a German multicenter study on intermittent versus maintenance neuroleptic long-term treatment in schizophrenia (ANI study) were reanalyzed with respect to the prevalence and profile, nature, time course, and predictive value of prodromal symptoms in impending relapse. The results demonstrate that prodromes are a category of symptoms on their own, but they share variance with other symptom domains. Treatment side effects, psychotic symptoms, dysphoric mood, and social dysfunction are all associated with prodromal states--the direction of this association, however, is still to be clarified. Prodromal symptoms are also related to the neuroleptic treatment strategy and its relapse-preventive efficacy--findings that underscore neuroleptic maintenance medication in preventing both overt and subthreshold psychotic morbidity in schizophrenia.

Prediction of neuroleptic on-drug response in schizophrenic in-patients by EEG.

SummaryThe subjects were 34 acutely ill in-patients who met the RDC criteria of schizophrenic psychosis, and 4 EEGs were recorded from each patient before, 2 h and 24 h after oral intake of a single dose of 150 mg perazine, and on the 28th day of the neuroleptic treatment period. As a criterion of clinical response a decrease of at least 66% in the schizophrenia-specific sum score of the Brief Psychiatric Rating Scale on day 28 relative to the baseline value was decided upon. The EEGs were assessed using a newly developed procedure which takes into consideration 4 derivations simultaneously. As we tried to search out EEG variables with predictive value the statistical data analysis underlying our findings should largely by regarded as exploratory. Independent of day, responders (R) showed a tendency towards more low voltage desynchronized epochs (non-A stage) than non-responders (NR). Thus, R exhibited a higher degree of dynamic variability or a broader range of control of the spontaneous vigilance fluctuation (dynamic lability) than NR (dynamic rigidity). Furthermore, R and NR differed with respect to their time-dependent changes of non-A epoch frequencies before medication. While R showed a monotonous increase which is typical for normals, NR did not. Because of considerable inter-individual variability these group differences could not be used for individual prediction of the therapy response. By means of a qualitative data analysis R could be distinguished from NR with regard to various test dose-induced changes of the topographical distribution of absolute alpha power. All the group differentiating variables showed a time course of the same kind: R showed a prompt and ample deflection and the same recovery of baseline; NR, in contrast, showed no significant deflections at all. These findings are in line with the results concerning the dynamics of vigilance and certain claims of earlier authors according to which EEG changeability should be decisive for therapeutic outcome. The prediction power could be enhanced considerably by means of a classification procedure for qualitative data, which allows a combination of two variables. Allowing the three qualities increase, decrease and no change a combination of two variables rendered 32 = 9 possible answer patterns, the individual patient showing only one of these patterns, of course. A correct classification of 26 out of the 34 patients (76.5%) was achieved by 12 different 2-fold combinations of variables. Eventually, we tried to base an individual prediction upon a multitude of selected, clearly response predicting answer patterns. We were governed by the idea that a patient who shows the total number of the response predicting answer patterns, can be regarded as R with much higher probability than a patient who shows only half the number or even none of them.

Outcome and risks of ultra-long-term treatment with an oral neuroleptic drug

SummaryIn 33 schizophrenic patients treated continuously as outpatients with perazine over two decades, the rehospitalization rate decreased from 0.58 before treatment to 0.07 during treatment. The intensity of psychopathologic symptoms and the side effects were found to be remarkably low. The high intraindividual constancy of perazine plasma levels and the tight correlation between dose and plasma levels indicated satisfactory patient compliance. Plasma levels amounted to only 25% of those under acute treatment and correlated positively with the severity of the disease. Higher plasma levels coincided with more frequent side effects such as slightly pathologic liver function and moderate impairment of oral glucose tolerance. The results suggest that low-dose maintenance treatment of schizophrenic patients with oral neuroleptics is effective and relatively safe.ZusammenfassungBei 33 schizophrenen Patienten, die seit durchschnittlich 18 Jahren kontinuierlich ambulant mit Perazin behandelt wurden, sank die Rehospitalisierungsrate pro Jahr von 0,58 vor auf 0,07 während der Behandlung. Die Intensität der psychopathologischen Symptomatik sowie der Nebenwirkungen waren bemerkenswert gering. Die hohe intraindividuelle Konstanz der Perazin-Plasmaspiegels und die enge Korrelation zwischen Dosis und Plasmaspiegel sprach für eine befriedigende Compliance (Behandlungstreue) der Patienten. Die Höhe der Plasmaspiegel betrug nur etwa ein Viertel der Spiegel, die während einer Akutbehandlung gemessen werden, und sie korrelierte positiv mit der Schwere der Erkrankung. Je höher die Plasmaspiegel waren, desto häufiger waren Nebenwirkungen wie geringfügig pathologische Leberfunktion und eine mäßige Verschlechterung der oralen Glucosetoleranz.Die Ergebnisse legen den Schluß nahe, daß eine niedrig dosierte Langzeitbehandlung schizophrener Patienten mit oralen Neuroleptika effektiv und relativ sicher ist.

Diagnostische Differenzierungsfähigkeit von psychopathologischen Symptomen bei schwierigen Differentialdiagnosen

SummaryWe investigated the extent psychiatric illnesses can be differentiated by means of psychopathological symptoms. The present condition of 2269 patients was analyzed; they had been admitted to the Psychiatric Clinic of the Free University of Berlin during 1971–1976, as documented by the AMP (PAS) documentation system. The most frequent diagnosis in the sample was schizophrenia (32%), followed by neurosis (22%), affective psychosis (14%), addiction (6.7%), and organic psychosis (6.2%).We could demonstrate that even such diagnostic groups are usually discernible by symptoms, where the differential diagnosis is often difficult. Organic psychosis vs paranoid schizophrenia and depressive neurosis vs depressive psychosis can be determined, but manic syndromes in schizoaffective psychosis vs manic syndromes in affective psychosis are hardly discernible. The potential to differentiate, however, only pertains to diagnostic groups, since many individual patients cannot accurately be classified into diagnostic groups by psychopathological symptoms alone. Only a few symptoms are pathognomonic, and if there are pathognomonic symptoms characterizing a diagnostic group, only a few patients in this group show these symptoms. p]These results indicate, at least for the high number of patients without severe and typical symptomatology, that we must:1.Achieve better differentiation on the diagnostic axis ‘psychopathology’ by means of empirically derived syndromes instead of isolated symptoms.2.Use other diagnostic axes (like etiology and course) for differential diagnostic purposes.ZusammenfassungUntersucht wird die Frage, inwieweit sich psychiatrische Krankheiten mit Hilfe psychopathologischer Symptome unterscheiden lassen. In die Analyse einbezogen wurden die auf dem AMP-System dokumentierten Aufnahmebefunde von 2269 Patienten, die in den Jahren 1971 bis 1976 in der Psychiatrischen Klinik der Freien Universität Berlin aufgenommen wurden. Die häufigste Hauptdiagnose in der Stichprobe ist Schizophrenie (32%), gefolgt von Neurosen (22%), affektiven Psychosen (14%), Suchten (6,7%) und organischen Psychosen (6,2%).Wir konnten nachweisen, daß selbst solche diagnostischen Gruppen sich auf Symptomebene in den meisten Fällen unterscheiden lassen, zwischen denen sich häufig differentialdiagnostische Schwierigkeiten ergeben: so z.B. organische Psychosen versus paranoide Schizophrenien und depressive Neurosen versus depressive Psychosen, während dies bei manischen Syndromen bei schizoaffektiven Psychosen versus manische Syndrome bei affektiven Psychosen kaum möglich ist. Diese Unterscheidbarkeit bezieht sich allerdings auf die diagnostischen Gruppen; für den individuellen Patienten sind die Symptome zur Zuordnung zu bestimmten Diagnosen nur bedingt tauglich. Denn sehr wenige Symptome sind pathognomonisch, und soweit überhaupt pathognomonische Symptome für eine diagnostische Gruppe existieren, weist nur ein kleiner Prozentsatz der Patienten mit dieser Diagnose sie auf.Dieses Ergebnis unterstreicht die Notwendigkeit — und dies gilt in besonderem Maße für die Mehrzahl aller Patienten ohne eine schwer und typisch ausgeprägte Symptomatik —1.auf der diagnostischen Achse „Psychopathologie“ eine bessere Differenzierbarkeit mit Hilfe empirisch ermittelter Syndrome zu erreichen,2.neben dem psychopathologischen Querschnittsbefund noch andere diagnostische Achsen (wie z.B. Ätiologie und Verlauf) zur Differentialdiagnose zu benutzen.