East-Side story: The standardisation of psychotropic drugs at the Charité Psychiatric Clinic, 1955–1970

Studies in History and Philosophy of Biological and Biomedical Sciences 42 (2011) 453–466

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East-Side story: The standardisation of psychotropic drugs at the Charité Psychiatric Clinic, 1955–1970 Viola Balz, Matthias Hoheisel Institut für Geschichte der Medizin, Charité Centrum 1 für Human- und Gesundheitswissenschaften (ZHGB), Charité–Universitätsmedizin Berlin, Campus Charité Mitte, Ziegelstr. 10 (Hofeinfahrt), D-10117 Berlin, Germany

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Article history: Available online 19 July 2011 Keywords: History of psychotropic drugs Patient files History of the GDR Standardisation Translation

a b s t r a c t The present article illustrates the history of psychotropic drugs introduced in the German Democratic Republic (GDR) from 1945 onwards. We begin by examining the introduction of an anti-depressant and a tranquilizer at the university psychiatric clinic, Charité, in East Berlin. On the basis of patient files, we consider the monitoring routines, altered by the use of psychotropic drugs, and the difficulties that arose when these routines were translated into existing research programs. In the 1960s, attempts to evaluate the psychiatric practice were based on psychopathology whereas at the end of the 1960s there was a shift to ‘‘target symptoms’’. Ó 2011 Elsevier Ltd. All rights reserved.

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1. Introduction In this article we will investigate the attempt to standardize psychopharmaceuticals in a socialist state—the GDR. By ‘standardize’ we mean a process with multiple phases; the first step is to observe the differing effects of the drug and to translate them within the clinic into a unifying scheme. A definitive order is formulated in publications. During the second step, questionnaires are developed that require recognition by medical practitioners in various clinics. The use of these instruments creates a standardized practice that makes a comparison of the efficacy of a psychopharmaceutical in various clinics possible. Although there are many economic-historical studies on the development and application of standardized instruments,1 it is surprising that there is little research on the suggested process of clinical translation. As we demonstrate, this translation of practical knowledge to a clinic-specific scheme is central for the standardisation of clinical knowledge. In a case study of the introduction of imipramine and chlordiazepoxide at the Charité psychiatric clinic in the 1960s, we will illustrate how the first attempts at translation were based on a specific order—Leonhard’s psychopathology. First Leonhard’s psy-

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chopathology and his theory of psychoses and neuroses will be described in detail. On the basis of an analysis of the patient files we will detail the various ordering schemes that should have stabilized the effects of the two psychotropic drugs. We will discuss to what extent the translation of the drugs’ effects, which were documented in clinical practice succeeded in creating a unifying interpretative scheme. Thus our analysis demonstrates how therapeutic practices of drug administration at the Charité resulted in an idiosyncratic research language for psychiatric discourse at the time, which remained closely bound to the local traditions of knowledge. In the second part we will describe the attempt of Leonhard’s scholars to show that his psychopathology was not only a clinic-specific ordering scheme, but also a model of standardisation for the whole GDR. Next we will look at the internal discussions, in the GDR, of differing models of psychopathology that should be considered for the standardisation of psychopharmaceuticals. It was only after growing reception to foreign discourse that professionals in the GDR changed their attempts at standardisation. Leonhard’s standardisation model of psychopathology became increasingly precarious as the focus moved to a discussion of target symptoms.2

E-mail addresses: [email protected] (V. Balz), [email protected] (M. Hoheisel). For psychopharmacology see, for example, Healy (1997, 2002). ‘‘Target symptoms’’ usually mean those symptoms who are meant to be treated by the psychotropic drug, e.g. agitation.

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Unlike the well-researched approach in the capitalist West, professionals in the GDR based their use and standardisation of psychopharmaceuticals on socialist forms of production and a demand-oriented acceptance of psychopharmaceuticals. The availability of the various substances and the special conditions for the use of psychopharmaceuticals in the GDR will become clear in the following text. 2. When they draw the curtain 1961: the politics of drug regulation in the GDR Historically, the examination of the GDR pharmaceutical supply has focused on the inadequacy of the centrally planned economy. Our focus is the fate of practices translated into shared and standardized methods; however, we must also consider the availability of drugs. The Eastern Block was attempting to isolate their economic sphere from Western foreign trade and attendant profit-oriented drug production. It is interesting to look at the implicit rules followed by doctors and pharmacists in the GDR in their demand for the availability of psychopharmaceuticals.3 ‘‘In particular to be clarified is the question of which substances we can do without and which can be replaced by preparations from the socialist states. Which measures and self-commitments have been seized upon or suggested in order to bring about and to support the necessary production of these substances in the GDR or in the socialist states?’’4 With this question, the Chief Pharmacist of the Charité Psychiatric Clinic in the GDR, Ahrens, urged an ‘‘extraordinary meeting of the local liaison physicians of the clinic on the Störfreimachung of pharmaceutical substances.’’5 Störfreimachung described the GDR government’s intention to be independent from imported products from capitalist countries abroad. But did the GDR have sufficient resources of its own to produce enough of the new psychopharmaceuticals to replace those available on the international market? Since its foundation, the GDR had always created barriers to capitalist foreign nations. The competition between the differing political systems of West and East Germany in the 1950s led to a significant emigration of doctors and other qualified employees to the capitalist West.6 By the end of the 1950s, the brain drain and the related lack of doctors were dramatic. The emigration of qualified personnel that had profoundly weakened the health institutions of the GDR decreased after the Wall was built in August 1961 and only then could one speak of the independent development of East German psychiatry. The competition between the systems no longer dominated everyday work and the Ministry of Health made efforts to ensure that the remaining top figures, for example, Karl Leonhard, were provided with good labour conditions.7 In the GDR, the introduction and development of new drugs was integrated in a centrally planned drug market. But how was the cen3

trally directed introduction of new psychopharmaceuticals in the GDR accomplished? The Health Ministry’s declared policy was to reduce the range of available products and to redesign the drug market according to demand-oriented principles; thus, only medically necessary substances would be reverse-engineered.8 In the 1950s, the state had not regulated drug evaluation9; rather clinicians implicitly set standards for evaluating the therapeutic value and tolerance of preparations. The present article will show how influential GDR psychiatrists were given a wide scope by the government to construct a proof for efficacy of psychopharmaceuticals in the 1950s and 1960s. This centrally controlled reverse-engineering of already tested substances in a socialist state is essential for our research perspective that focuses on the influence of clinical scientists. The role of the pharmaceutical industry in the standardisation of efficacy, emphasized in the capitalist West, especially by U.S. psychiatrists, was of far less importance in the GDR. Thus, GDR clinicians’ involvement in commissioning drugs for manufacture, judging their clinical value, and determining if they should be imported, is illustrated by the example of chlordiazepoxide and imipramine at the Charité Psychiatric Clinic. The Committee for the Procurement of Therapeutic Agents was entrusted with addressing the need for these two medications (as with most available drugs) at this hospital. The committee included the so-called ‘‘local liaison physicians’’ (Verbindungsärzte), as well as pharmacists for both the Charité and state supply points for pharmaceutical products. The committee responded to the Health Ministry’s needs and plans to import pharmaceuticals for the clinic. In general, the clinic was to rely solely on pharmaceuticals from either the national manufacturers or from other Eastern Block countries. However, the demand for some medications could only be met by importing them from the capitalist West. For imipramine and chlordiazepoxide, dependence on local or Eastern Block suppliers affected material availability and the time required for standardisation. Let us take a closer look at these two pharmaceuticals. Imipramine was first internationally marketed as an ‘‘antidepressant’’ on the basis of clinical testing by Roland Kuhn.10 It had been produced, since 1957, in Switzerland by the Geigy Company under the trade name of ‘‘Tofranil’’ and was available in the West and the GDR from as early as 1958. By January 1959, it was being imported into the GDR and used at the Charité.11 In October 1961, imports of Tofranil were stopped and replaced by the Hungarian version of the drug, ‘‘Melipramin’’, and the policy of Störfreimachung was declared successful.12 In subsequent years, imipramine treatment at the Charité was substituted with Melipramin.13 In 1973, the GDR began to manufacture its own antidepressant, Pryleugan.14 The reason for this late entry into the manufacturing of an antidepressant was probably because of the initial and relatively reasonable availability of Melipramin from the GDR’s socialist brother, Hungary, which supplied most of the Comecon states (from 1949-1991 an economic organization of

Ernst (1997). HU (16.10.1961). 5 HU (16.10.1961). 6 Ernst (1997, S. 57–77). 7 Eghigian (2002, p. 365). 8 To assure the constitution of a demand-oriented assortment of drugs, on June, 1, 1960 the National Bureau for the supply of pharmaceutical technology (Staatliche Versorgungskontor für Pharmazietechnik—SVPM) was established as a organization in charge of ensuring the supply for the institutions in the public health and veterinary sector. Their functions were, among others, the organization of a (scientific) study for the assessment of demand and the coordination among the industry’s governing economic bodies, quality management, the drug industry’s design of their product lines, and to determine and ensure import needs (Eichhorn & Schröder, 1989, S. 44f.). 9 Klöppel (2009, p. 204). 10 Healy (1997, p. 48–53). The first publication of West German psychiatrists was released in 1959, see Zillinger (1959) and Poenseler & Krauss (1959). 11 Publications in GDR-Journals were entitled with the name of the Swiss product ‘‘Tofranil’’ for a substantial time period, see for example Aresin (1961) and Poussaint & Ditman (1965). 12 HU (o.A [10/1961]), p. 5. 13 In the patient files after 1961 we nevertheless find the Western brand name ‘‘Tofranil’’ from time to time. This could be due to a greater familiarity of the doctors with that name. But these findings also suggest the possibility of importing Tofranil, maybe in periods of deficiency. 14 Why the GDR-industry finally provided its own drug, is a question of current research. 4

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Eastern Block countries).15 From 1961 to 1970 doctors at the Charité seldom complained about a lack of Melipramin.16 The extent that the substance was available in other clinics or for out-patient treatment is unknown. The second pharmaceutical, chlordiazepoxide (Librium) was significantly restricted by the Störfreimachung economic policy. In a report on the ‘‘Development of Therapeutic Supplies in the Field of Sedatives and Hypnotics,’’ requests for Librium were answered thus: ‘‘As regards Librium, colleague Bertling has informed us, that on the basis of advice from expert groups the import of this substance has been rejected, as we can expect no acute danger to human life, due to the failure to obtain this drug.’’17 The need for this substance did not fulfil the criteria for capitalist imports. Compared to imipramine, however, there was no ‘‘socialist generic’’ for chlordiazepoxide. Hoffman-La Roche produced ‘‘Librium’’ in Switzerland starting in 1960. By the beginning of 1963, a call for ‘‘the development of substances with Librium-like effects’’ appeared in the records of the ‘‘Working Group for Synthetic Drugs’’ of the Ministry of Health.18 In the fall of 1967 the Arzneimittelwerke Dresden (Dresden pharmaceutical plant) finally began producing chlordiazepoxide under the trade name of ‘‘Timosin’’ and in 1969, changed the name to ‘‘Radepur.’’19 These processes highlight the research-policy of the Ministry of Health, which despite doubtful evaluation of the product’s usefulness, was determined to make the product available in the GDR. Nevertheless, resources in East Germany were limited and the government was forced to set priorities. The files of one of the most important producers of psychotropic drugs, the Arzneimittelwerke Dresden, document that at first the plant subordinated the reverse-engineering of tranquilizers for the synthesis of anti-depressants. One of the plant’s employees stressed in his travel account in 1964: ‘‘4 to 5 years ago, we had the impression in the GDR that this field was not so much a focal point anymore, and as our research capacity is limited, we work on anti-depressants abandoning the domain of the minor-tranquilizers.’’20 At the psychiatric clinic of the Charité, chlordiazepoxide was not particularly promoted either. In February 1961 at a meeting of the Committee for the Procurement of Therapeutic Agents, Chief Pharmacist Ahrens emphasized the ban on samples from the West and called for a controlled use of psychochemicals available in the Federal Republic of Germany (FRG): ‘‘The clinics are always receiving test models from West German and foreign companies. The clinic directors are thus requested to name the new preparations that can be considered useful, that they can be added to the GDR’s 1962 import list, for example Librium Roche, Dianabol Ciba, Ismilen Ciba etc.’’21 By late 1961 restrictions on imports had tightened. In October of that year, when the psychiatric clinic presented a ‘‘wish list’’ of pharmaceuticals to the Committee, there was no mention of Librium. Contrary to demands for an efficient supply of a preparation from the GDR production lines, the doctors of the psychiatric clinic made no special efforts to obtain chlordiazepoxide. Can the lack of demand for chlordiazepoxide be explained simply by the lack of a budget for medication? To understand the use of drugs and the lo-

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cal attempts at evaluation more fully it is necessary to look at the structure and employees of the clinic. 3. The Charité psychiatric clinic in the 1960s Since 1957 Karl Leonhard directed the academic psychiatric hospital of the Charité. His work and the importance of his psychopathology to the attempts at pharmaceutical evaluation will be explained later in detail. Under Leonhard’s directorship the clinic was divided into specialized departments, including a children’s department, a psychotherapy ward, and expanded with the addition of diagnostic and laboratory facilities. A close look at the division of beds in the psychiatric clinic shows that more than half (171) of them were reserved for psychiatric patients in a strict sense, 74 for neurological patients, and 54 for patients receiving psychotherapy. The consequence of this differentiation in departments was that one senior doctor (Oberarzt) no longer held responsibility for a single ward. Rather the seven Oberärzte in the clinic had to look after several wards at the same time. For example, the first senior doctor, Dimitros Fotopulos, was responsible for wards 2, 3, 6, 7, and 8. Barbara Elisabeth Bergmann, though actually superintendent of psychotherapy, also worked in wards 1, 3, 6, and 8. Heinz A. F. Schulze, who was also the liaison physician for medication issues, and did his training in neurology, looked after both the neurological ward 2 and psychiatric ward 3. How can we explain the overlapping responsibilities of the doctors? One reason was the lack of qualified doctors, and this continued to be a problem even after the construction of the Wall; only 6 of the 22 assistant doctors had a formal qualification in psychiatry.22 So a possible explanation is that senior doctors were always available for the wards that lacked a qualified physician. Even though the number of qualified doctors in the clinic, from today’s perspective, is not particularly low, there were immediate complaints about the lack of senior doctors. In a letter to the dean of the university, Leonhard sharply criticized this malpractice: according to him, the clinic needed at least three more posts for doctors, because at that time the doctors had responsibility for not only 13 clinical wards but also for seven diagnostic departments and one polyclinic. The polyclinic alone needed five posts for doctors.23 The problems that arose in the clinic because of the lack of qualified personnel became more acute due to the severely limited budget for drug therapies: in total psychiatry had 9000 DM per month at its disposal for more than 300 beds which represented approximately 30 DMs per patient.24 If one takes into account that the cost of an average Melipramin treatment was more than 1 DM per day, it is clear that the budget for medication was far from adequate.25 Actually in a letter about planning to the dean, Leonhard noted that the clinic overspent its monthly budget by approximately 2000 DM—almost a quarter of the entire monthly budget. Did the limited resources essentially control the use of psychopharmaceuticals? In a closer look, this thesis cannot be substantiated. Though the clinic requested an increase in their medication budget for 1964, it

15 HU (o. A. [09/1962]): ‘‘It was noticed that the supply of imported drugs improved considerably. In the most cases the delivery occurred in the amount of the plan figures.’’ See also HU (o. A. [08/1963]): ‘‘The neuropathic clinic was supplied according to the plan with Melipramin Drag (. . .).’’ 16 An exception is the temporary shortage in the beginning of 1963. The following note was found: ‘‘The neuropathic clinic complained that the patients in the GDR are not adequately provided with Melipramin Drag.’’ MFG (27.02.1963). This shortage seems to be removed by the mid-1960s, as another note shows. See MFG (30.08.1963). 17 MFG (3.12.1961). 18 MFG (18.4.1963). 19 Anonymous (1967). 20 AWD (10.03.1964). 21 HU (o.A. [02/1961]). 22 IGM (01.07.1963). 23 IGM (01.07.1963), Anhang Betr. Stellenplanerweiterung für Ärzte 24 IGM (01.07.1963). 25 Vgl. Arzneimittelverzeichnis (1965, S. 183). A treatment consists of 6–10 pills daily. The bulk pack (200 pills) cost 23,05 DM.

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justified the increased requirements with the increase ‘in patients with inflammable diseases, most of all those with a serious encephalitis [acute infection and inflammation of the brain], as well as the increased admission of patients with a progressive paralysis [. . .].’ Therefore it had become necessary ‘to prescribe increasingly penicillin, antibiotics and sulfonamide as well as Predison preparations.’26 The doctors administered up to 1 million units of penicillin a day for the successful treatment of progressive paralysis over a period of two to three weeks.27 If one realized that this treatment required, on average, 10 DM per day the complaints of the clinic director quickly become understandable.28 The use of new psychopharmaceuticals, in itself, did not seem to necessitate a budget increase. Their use in the context of Leonhard’s psychopathology was rather restrained. But how can we explain their frugal use if the lack of resources was not the primary reason? 4. A botanical garden of illness: the psychiatric clinic as an observation theater for standardisation research To understand the work in the Charité clinic and the first attempts at psychopharmaceutical evaluation, we will now look at the theoretical position of the clinic. The detailed description of Karl Leonhard’s psychopathology demonstrates an attempt at clinical standardisation that in the 1960s was still oriented towards fundamental individual diseases. Therefore we will now explain the psychopathology of Leonhard, and especially his theories of psychoses and neuroses in detail. Next we will describe how this psychopathology was a co-determinant of psychopharmaceutical evaluation. Karl Leonhard, one of the most well known GDR psychiatrists, was able to achieve a level of recognition in the West German scientific community with his research on the classification of endogenous psychoses. A primary goal of Leonhard’s work on psychiatric illnesses was formulating an exact prognosis based on the diagnosis.29 He relied particularly on the long-term observation of patients, many of whom he examined over the course of decades. In the tradition of Karl Kleist, Leonhard developed a system for diagnostic description that included numerous subgroups. This method of diagnosis was distinguished by a rigid demarcation among diseases to which he ascribed highest priority. The approach was intended to go beyond Kraepelin’s principle dichotomy of psychoses—manicdepression and dementia praecox.30 Leonhard categorized a series of so-called marginal psychoses which, lying between two poles, he labelled as ‘‘cycloid psychoses.’’ These diseases were characterized by particularly intense psychotic episodes accompanied by complete, gradual regression.31 For Leonhard these cycloid psychoses were specifically treatable with drugs.32 Leonhard separated schizophrenias into two large groups as well. Here he drew a dividing line between unsystematic schizophrenias with a positive prognosis and systematic schizophrenias, which appeared to result from

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a basic defect or damage.33 In the case of a systematic schizophrenia he considered all therapeutic efforts to be futile.34 The ‘‘phaseal psychoses’’ presented a central indication for imipramine treatment and using this as a criterion, Leonhard created a category of endogenous psychoses including psychoses that many psychiatrists of the time classified as manic-depression. For Leonhard these were not simply bipolar disorders but rather a series of mono-polar disorders like melancholy, mania, depression, and euphoria.35 This categorical systematization of psychiatric illnesses thus determined not only clinical work but also the research agenda. In the next two sections we will take a closer look at the treatment of psychotic and neurotic diseases. In the history of psychiatry, the classification of psychiatric diseases in the tradition of Wernicke, Kleist, and Leonhard has been described as the school of ‘‘splitters.’’ They form the counterpart to the ‘‘lumpers,’’ who, according to psychiatrist, Christoph Mundt, are bound to the tradition of Eugen Bleuler’s classification system.36 Both concepts borrow from the descriptive system of botanical taxonomy. The systematizing and standardizing of biological entities occurs either by means of the narrowest, most precise classification scheme possible (such as the ‘‘splitters’’ practice), or it can be carried out within a system for which broad concepts are applied to classify a large variety of species (as the ‘‘lumpers’’ understood it). Research at the Charité clinic was thus informed by a process of long-term, clinical observation and subsequent translation into a system of narrow diagnostic classifications. Now, using the examples of imipramine and chlordiazepoxide, we turn to the efforts to translate clinical practice into a system of clinical research. 5. Imipramine and the leonhard endogenous psychoses In this section we explore the first experiences with the new anti-depressant, imipramine in the Charité clinic. How did Leonhard’s teachings connect to a standardized description of the efficacy of the new drugs? To answer this question we will first look at the programmatic publications on imipramine by Heinz A. F. Schulze. Next we will reconstruct the use of the drugs on the basis of the files from the Charité clinic. Finally we will describe a case study, extensively analysed in one of the publications of the time, to demonstrate how practice, as documented in the files, was translated in the publications. Which additional statements can be found in the files? What notation systems were used to document practice? First we will more fully explain the position of Heinz A. F. Schulze in the Charité clinic. Schulze, member of the Charité Committee for the Procurement of Therapeutic Agents had been employed at the psychiatric clinic since 1957; in 1961 he became senior physician.37 He had begun his clinical work at the psychiatric hospital just before Karl Leonhard’s 1958 appointment at the Charité and continued his work as a physician and later head of the clinic until 1987.

IGM (01.07.1963). Harrer & Sommer (1974, S. 507). 28 In the Arzneimittelverzeichnis (Index of medicines for GDR) 500.000 IE penicillin G produced by «Jenapharm» are listed with 4,95 DM (vgl. Arzneimittelverzeichnis, 1965, S. 217). 29 Leonhard (1957, p.364). 30 Leonhard (1957, p. 359f). 31 Leonhard (2003, p. 63). 32 Leonhard voiced this opinion in a letter to his American colleague. He pointed out that ‘‘with cycloid patients a somatic treatment accelerates the success’’ HU (17.05.1962). 33 Leonhard (2003, p. 86). 34 ‘‘With the systematic forms, in my opinion, all treatment forms are futile. At best they will alleviate the condition short-term, but the process continues independent of treatment’’ HU (17.05.1962). 35 Leonhard (2003, p. 6). 36 Mundt (2005, p.10f). 37 This information is taken out of the Humboldt-University’s Staff Directory and University Calendar. See Personal- und Vorlesungsverzeichnis der Humboldt-Universität Stdj. (1959/60, HeSe: p. 55), Personal- und Vorlesungsverzeichnis der Humboldt-Universität: Stdj. (1961/62, HeSe: p. 69); in 1976 Schulze followed Karl Seidel as a director of the clinic. 27

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Schulze established himself as the psychiatrist ‘‘who represents psycho-pharmacology at the local clinic’’.38 Even if we assume that he still had to manage clinical supplies with the director, it is nevertheless striking how Leonhard restrained himself. Schulze conducted all congresses and planned psycho-pharmacological research, often with the help of younger colleagues.39 Schulze was a loyal supporter of Karl Leonhard’s psychopathology. Without doubt, it was Schulze’s central goal to connect Leonhard’s differentiated pathology with the evaluation of the new psychopharmaceuticals, as his first article on imipramine makes clear. In 1964, Heinz A. F. Schulze and his colleague Jochen Neumann published the results of the first use of Melipramin (imipramine) in the Charité based on treatments between 1962 and 1963.40 In their report the authors attempted to relate the effectiveness of imipramine for the differentiated categories of psychoses according to the Leonhard research paradigm. (For an overview of the classification of endogenous psychoses according to Leonhard and the individual sub-groups see Fig. A). First we explain the research program noted in this and other articles by Neumann and Schulze. Right from the start of the published articles, the authors demonstrated their epistemological interest. A targeted drug therapy, they argued, requires a precise differentiation between various forms of psychoses. Therefore in order to employ the most appropriate therapy possible for each respective disorder, a differential diagnosis is necessary. Nevertheless the authors interestingly failed to develop separate treatment options in regard to these disorders. Secondly they hoped to employ imipramine as an aid for differential diagnoses to support the diagnostic process in undetermined cases.41 The publications of Neumann and Schulze joined a series of publications that addressed the issue of using a variety of psychotropic drugs to help achieve a better classification of psychoses.42 In the following years, Schulze and Neumann developed their argument further.43 ‘‘The different, prognostic characteristics of phaseal and cycloid psychoses postulated by Leonhard on the one hand and schizophrenias on the other were confirmed.’’44 The fine-tuning of their own diagnostics, by observing the effect of individual psycho-pharmaceuticals on their patients, characterised Schulze and Neumann’s research throughout the 1960s. But how did the two authors translate their clinical experiences with imipramine into research results and make them accessible to other psychiatrists? Drawing on Leonhard, they argued that the representative picture of the special case allows for the most precise description possible. The individual nuances of the psychiatric disease condition served as an example for the treatment of further cases.45 Schulze and Neumann actually presented the research results in their first publication on imipramine casuistically as well; individual medical histories offered proof of the effectiveness of a psychopharmaceutical.

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Now we take a closer look at Neumann and Schulze’s first publication on imipramine (1964). The treatment cases described by the authors are divided into four groups: first the phaseal psychoses; second the cycloid psychoses—fear-joy psychosis and arousedinhibited amentia; third, a subcategory included unsystematic schizophrenias; and finally the fourth group of systematic schizophrenias. In conclusion, the authors describe miscellaneous cases treated with imipramine, including reactive depressive mood disorders. The vast majority of imipramine treatment was given to patients labelled psychotic, approving that the etiology was endogenic. Depressive disorders such as reactive depression, depressive neurosis, or neurasthenia were not mentioned. In their 1964 report, the Berlin psychiatrists offer the most detailed description of patients with a manic-depressive disorder. In a publication in 1966, Schulze and Neumann contested that imipramine not only improved depressive symptoms but also increased expression of the other end of the disease pole, mania.46 Schulze and Neumann relied heavily on casuistic arguments in their research and declared their clinical descriptions were a principle of standardisation at the same time. For this reason it is worth taking a closer look at the 1962 patient records. When we compare the patients analysed in the articles with all the patients treated with imipramine in 1962, it is striking that imipramine use was restricted to the psychoses listed above.47 Thus in 1962, two thirds of all patients treated with imipramine were classified as phaseal psychoses, and nearly half of those were diagnosed as manic-depressive.48 The cycloid psychoses also formed a large treatment group, particularly for patients with amentia. No patients with unsystematic or systematic schizophrenia were treated with imipramine, and nonpsychotic diagnoses were rarely found. For an overview see Fig. B. Considering the total number of patients with an endogenous psychosis who were treated in the clinic, it becomes evident that the psychiatrists only used imipramine therapy with a minority of their ‘‘psychotic’’ patients. Barely a quarter of the manicdepressive patients received the drug, a third of the patients with pure melancholy and other depressions, and rarely for the rest of the patients with other psychoses.49 Nearly all the imipramine treatments were conducted in the psychiatric wards 3 or 7.50 In ward 3, Heinz A. F. Schulze was active as senior physician, which makes the skewed proportion less surprising.51 The researchers treated psychoses primarily with imipramine, while neurotic and other reactive depressions, in contrast, were only rarely treated with this drug. It appears that Schulze and Neumann were oriented toward Leonhard’s position regarding drug and somatic therapies. Early in the 1950s, Leonhard had declared that a precise diagnosis was indispensable before starting a treatment and according to him, only psychoses required somatic

HU (2.6.1966). See for example Neumann & Schulze (1964), Schulze & Neumann (1966a, 1966b), Schulze (1968, 1969) and Schulze (1970). 40 Neumann & Schulze (1964). 41 Neumann & Schulze (1964, p. 438). 42 The English psychiatrist Frank Fish first suggested in 1964 that the Leonhard classification scheme of psychoses makes it easier to employ the different narcoleptics in a more custom-fitted manner (Fish, 1964). 43 Schulze & Neumann (1966a, 1966b) and Schulze (1969). 44 Schulze & Neumann (1966a, p. 180). 45 Neumann & Schulze (1964, p. 438) and Schulze & Neumann (1966a). 46 Schulze & Neumann (1966a, p. 180). 47 In 1962 however not all treatments under the name of Melipramin were documented. In just a third of the cases the Swiss trade name Tofranil was used. Whether this documentation practice can be traced back to the fact that many doctors simply continued to use the name Tofranil or to be understood as an indication that a ‘‘Störfreimachung’’ for the Melipramin production actually didn’t succeed cannot be reconstructed. 48 Many patients with the diagnosis manic depressive disorder received a combination treatment with Propaphenin (Chlorpromazine). 49 The total number of patients treated can thus be summarized according to diagnosis in the year 1962: manic depressive disorder 6/28; other depressions 6/35; pure melancholy 2/7; angst psychosis 1/32, amentia 4/26. 50 In ward 3 there were 10 patients treated and in ward 6 there were 8. In station 6 Dr. Seige’s patients were frequently treated with Melipramin. Seige did not publish on psychpharmaceuticals. In a HU archive there is correspondence from Karl Leonhard with a Hungarian colleague, reporting that Seige obtained LSD for self-experiments. See HU (07.10.1958). This suggests at least a certain interests in psychotropic substances. 51 What the file documentation suggests is that Schulze did not treat all the patients himself. 39

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therapy. The therapy would work best with the unsystematic schizophrenias and the cycloid psychoses. The worse the prognosis of these diagnoses, Leonhard concluded, the more seriously an invasive therapy should be considered.52 When we take a closer look at patients treated with imipramine, the Berlin doctors appear to have given their boss’s guidelines only brief consideration. As exhaustively described in the publication, the doctors did not treat only psychoses with a bad prognosis. The phaseal psychoses, whose course according to Leonhard could not be given a clear prognosis, were actually treated most frequently with the new anti-depressant. There were indeed a few patients with cycloid psychoses who were treated with the drug, but nowhere in the sample is there a schizophrenic patient who received such treatment. In their article Schulze and Neumann made it clear that they considered imipramine to have far fewer side effects than phenothiazines, for example.53 This may have been a reason for using the antidepressant more broadly for patients with psychoses than say, using chlorpromazine. It is still interesting, however, to examine the files of the documented medical histories further. Only then is it possible to understand the casuistic perspective that the two authors use to underpin their descriptions. It is remarkable that in the medical histories, the relationship between diagnosis and therapy in practice is not as clear as the published articles and our quantifying analysis would initially suggest. The precise notes in the medical records show that it is impossible to determine a clear disease category that provided a starting point for the treatment with imipramine. There was no support for the authors’ claim that therapy was used to further differentiate the still unclear diagnosis (on the basis of the effects of a variety of drugs). The drug treatments in the clinic, rarely recorded in detail, actually seem to have been performed according to criteria other than those suggested in the published articles. Interestingly though, the argument in the published article relied heavily on individual cases. The patient that Schulze and Neumann described in greatest detail, a 64-year-old pensioner, can be reconstructed on the basis of the clinical record. This patient however, who was treated by Schulze, had a file that is notable for the detailed documentation and should thus be described more extensively.54 As we learn from his dossier, the patient S. was admitted in late1962 and exhaustively questioned by Schulze. At first the patient described mostly physical symptoms, which led to an initial diagnosis of ‘‘suspicion of frontal brain tumour’’.55 Despite more exhaustive examinations, over time, the treating psychiatrists were unable to find any organic reason for the patient’s complaints, which included a dry throat that increased steadily. The doctors now described the patient as ‘‘very inhibited,’’ and so in a later visit on December 12th Leonhard called the old diagnosis into question. Whether the patient was manic-depressive or ‘‘only’’ a hypochondriac could also not be definitively answered in this examination, six weeks after being admitted to the clinic. On December 18th the psychiatrists began imipramine treatment, initially with a low dose and then increased to 350 mg, as documented in the patient’s chart.56 In the observational notes however this therapy was not mentioned at all. In the doctor’s letter, Schulze noted that the diagnosis of ‘‘endogenous depression’’ had lead to the indication that the patient be treated with imipramine;57 in the medical file, however, this diagnosis is not recorded. From January 4th and forward the 52 53 54 55 56 57 58 59 60

Leonhard (1956, p. 292). Neumann & Schulze (1964, p. 465). PUB, PF 664/62. PUB, PF 664/62, Exploration. PUB, PF 664/62, documentation of drugs. PUB, PF 664/62, doctor’s letter. PUB, PF 664/62, progress report 04.01.1963. Neumann & Schulze (1964, p. 441). Schulze & Neumann (1966b, p. 12).

psychiatrists reported only that the patient had a series of delusions with great sensual clarity.58 While Schulze and Neumann concluded in their article that these delirious symptoms were due to the preceding imipramine treatment,59 however, in the dossier this reasoning is not documented. During medical rounds on February 11th patient reported feel significantly better and free of pain for the first time. Finally on February 28th, imipramine was mentioned in the observational notes for the first time. The file noted that after the imipramine treatment it appeared that the patient had been altered: ‘‘he is friendly, open, and interested in life again.’’ Four weeks after the doctors took him off the drug, they concluded that the patient was now ‘‘somewhat cheerful.’’ Only at the end of hospitalisation the diagnosis of ‘‘depressive phase of manic depressive disorder’’ first was made. In the epicrisis Schulze states that the patient’s medical condition had improved rapidly for the better. The case described here is notable and serves as an example of how the researchers constructed knowledge about an individual case. In the case of patient S., the Berlin psychiatrists did indeed succeed in substantiating the diagnosis of manic-depressive disorder. The fact that the patient was cheerful after receiving the drug, however, was the only hint of a bipolar disorder. When we compare patient S.’ file with those of other ‘‘manic depressive’’ patients in the test group from the year 1962, the case described was special as there were no recognizable or comparable efforts to make a clear diagnosis by using a drug. Even in the files, extensively referred to by Schulze and Neumann in their published article, remarkably little information is documented for imipramine. If it was the intention of the two psychiatrists, to employ drugs to standardize both psychiatric diagnoses, as well as the indication for use of the drugs, then the interested reader must wonder why the observed symptoms and the course of the drugs in interesting cases were not documented. Although the published article of the two authors clearly provides the patients’ medical histories as their reference source,60 after reading the files we are left with the impression that these only served in part as reference sources. The authors’ implicit knowledge appears to have had a role in their argument. Schulze and Neumann appear to have concentrated on a precise description of the psychiatric disease pattern, even when the medical record does not document in detail how the psychiatrists came to their individual diagnosis. This begs the question of how serious the authors were about employing imipramine to achieve more precise diagnoses. In the medical records there are no clues that refer to the postulated efforts at standardisation, although the published research draws extensively on the patient records. There are also no tables, blank sheets, or even simply detailed notes that would suggest an interest in systematizing the effects of psycho-pharmaceuticals. On the basis of the described medical records, this demonstrates a gap between the interests noted in the published article and those of the actual, psychiatric (documentation) practice. Was the course of observation actually focused on the disease progression that Leonhard considered so important and that the doctors were supposed to learn to document properly? And did this leave insufficient time for local drug research efforts, such as those of senior physician Heinz A. Schulze? Was the interest in the new psychopharmaceuticals really

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great enough to leave traces in the everyday documentation practices of the clinic? Or was the standardized survey of psychopharmaceuticals, according to the model of Leonhard, in the last instance, only a particular interest of Schulze that did not garner the interest in the rest of the clinic psychiatrists? The contradictions of clinical practice and the power of Leonhard’s approach in structuring therapeutic practice will be discussed further, using the example of the tranquilizer, Timosin. First, however, we discuss Leonhard’s underlying theory of neurosis. 6. A systematic approach on how to treat a neurotic person In his textbook, Individualtherapie der Neurosen (individual therapy of neuroses), Karl Leonhard presented a systematic introduction to his theory of neurosis. The history of this instructional text illustrates one facet of Leonhard’s work, which he pursued until his retirement in 1970. In 1959 after Leonhard had formulated the theoretical outlines, he and his closer colleagues began working together on an expanded 1965 edition of the book.61 In this work the authors focused on case studies, to allow for an improved differential diagnostic classification of ‘‘neurotic disturbances.’’ Leonhard argued, despite a reciprocal conditionality from outward influences and constitutional processing that ‘‘[. . .] in general the type of neurosis is indeed more determined by the inward structure of the person [italics added] than by outward occurrences.’’62 Thus, for the diagnostic clarification of the course of a specific illness, the patient was first assigned to a category of ‘‘primary personality.’’ On the basis of information given in the case history, the patient was then classified as either ‘‘hypochondriac,’’ ‘‘anankastic,’’ or ‘‘hysterical.’’ After further observation ‘‘accentuations of the personality’’ and the patient’s ‘‘resonant rise of affects’’ were considered significant.63 The highly differentiated, idiosyncratic taxonomy was visible in this instructional work, as an analogue to the classification of endogenous psychoses. Although Leonhard intended to use psychoses and its subforms as targets for antidepressants and neuroleptic drugs, in therapy for neuroses he soundly rejected the use of psychopharmaceuticals. Rather, he considered a systematization of talking therapy. ‘‘A very significant feature of my psychotherapy, as I see it, is that the treatment does not simply operate on the patient, but rather that the patient himself works along with the treatment. That means basically that under our guidance he effects a healing of himself. Passive methods of therapy, sedatives, tranquilizers [. . .] therefore have no place in my therapy of neurosis.’’64 For Leonhard then, the insistence on a form of ‘‘active treatment’’ was not compatible with the use of pharmacological treatment measures.65

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A systematic evaluation of the most important medical journal in the GDR from 1955-75 confirms this. Within the broader sphere of the Leonhard clinic, we find a few publications that are critical of the pharmacological treatment of neuroses, but there are no studies concerned with the effectiveness or classification of chlordiazepoxide or other related substances in their diagnostic-therapeutic uses.66 Thus there is significant evidence that in the published material, chlordiazepoxide was perceived as a disturbance factor for accurate diagnosis. When clinicians tried to diagnose a neurotic development or discuss standardizing therapeutic interventions, there was no mention of chlordiazepoxide or similar drug. 7. Symptoms, sleep and the pragmatics of sedation It seems likely that, behind the Iron Curtain, benzodiazepine drugs would challenge academic psychiatrists working in the relatively young field of neurotic illness.67 When chlordiazepoxide was introduced for ‘‘neuro-vegetative disturbances’’68 in the GDR, the field of neuroticism became an area of research for the drug.69 Why then, under Leonhard, did no such translation of the clinical usage into research for neurotic disorders occur? On the basis of medical files we attempt to tie this question back to the meaning that was then attributed to the use of chlordiazepoxide.70 Was this drug even used in the clinic at all? Were the decisions made in a routine manner? First we examined how the usage of chlordiazepoxide within the clinic might have differed.71 In Fig. C the treatment cases we examined are itemized according to primary treatment diagnosis as well as the ward where the treatment took place.72 The initials of the patients who received chlordiazepoxide are also listed, according to their diagnosis and the ward where they were treated. What the files reveal, is that the individual wards, supervised by several senior physicians, had distinct emphases. The neurological part of the clinic, ward 1 and ward 2, was the location for the treatment of a large number of patients. Schulze, the senior physician in ward 2, treated a few of his patients with chlordiazepoxide. In ward 6, a psychiatric ward led by Frau Prof. Bärbelies Bergmann, patients with the entire spectrum of psychiatric disease were treated. Of particular interest is ward 5, a psychotherapeutic ward, where female and male patients were treated mainly with psychotherapy. The responsible senior physician there was Dr. Ilse Müller who was generally assisted by Ellen Sitte, a trained psychologist.73 In this ward Karl Leonhard was also closely involved in the clinical care of patients.74 In total 9 of 91 patients (9.9%) who were treated with chlordiazepoxide in 1968. There is, however, no direct reference made to the

1st edition: Leonhard (1959), 2nd edition: Leonhard et al. (1965). Leonhard et al. (1965, p. 11). 63 Dickson (1988), Anonymous (1973). 64 Leonhard et al. (1965, p. 16). 65 This holds also for a later time period, as the 3rd edition of Leonhards book revealed. Leonhard & Berendt (1981, p. 14f). 66 See e.g. these publications from Charite researchers: Haas (1968) and Leonhard (1968). 67 When Chlordiazepoxide became available in the GDR, this process had already taken place in the Western world, see Jenner & Kerry (1961). 68 Anonymous 1967. 69 For trials in the GDR see Kühne (1966), Anonymous (1967) and Leonhard & Bergmann (1964). 70 Risse & Warner John (1992, p. 186). 71 The analysis draws on a sample of 91 files, representing approximately 10% of files for the time period of this study. Criterion for inclusion in the sample was psychiatric clinic treatment over at least one day in the period from July–December 1968. This meant research on the practice of administration about one year after its introduction. For this time period, medicament supply was not disputed at the Committee for the Procurement of Therapeutic Agents, thus we assume it was sufficient for demand. 72 A statistical assessment of diagnoses entails some problems that cannot be discussed in detail here. The numbers often do not account for every problem seen and treated at the psychiatric clinic.We tried to classify the primary reason for treatment at the clinic. Additionally we recorded every notion of addiction problems and neurotic ‘‘add-on’’ diagnoses. When performing statistical analysis, we supplemented it with additional examination for addiction problems and neurotic diagnosis. Anna B., who was primarily treated for a psychotic illness was the only patient, who was also given a diagnosis of a neurotic illness. We account for that with the qualitative description of the case. 73 In a popular magazine of science, Müller presented the clinic’s concept for the treatment of the ‘‘Modeerkrankung vegetative Dystonie’’, see Müller (1968). 74 See Atzl, Hess, and Schnalke (2005). 62

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treatment diagnosis and the actual use of the drug. What appears instead is evidence that cases treated with chlordiazepoxide did not belong to a particular illness group but rather seem to be distributed across all groups treated in the psychiatric clinic.75 What also stands out is that this distribution of chlordiazepoxide-treated patients seems to correspond to the wards where they were treated. In wards 1 (neurology men) and 6 (psychiatry women) the greatest numbers of chlordiazepoxide treatments were performed. In wards 7 and 8 (psychiatric wards for men and women) on the other hand, there were no treatments with the drug. Seen on the whole it can be emphasized that patients in the classical psychiatric wards were more often treated with chlordiazepoxide, independent from the diagnosis, than, for example, in the psychotherapeutical wards. The variable significance of this drug treatment becomes even clearer when we look at the duration of the treatment (Fig. D). The psychiatric ward 6, lead by Frau Bergmann, who had apparently developed a preference for the drug, accounted for 80% of all chlordiazepoxide treatment days. In the psychotherapeutic ward 5 however, Mrs. Müller’s domain, this treatment was strictly avoided.76 What clues do the medical files give about the motivation for chlordiazepoxide use? The most striking finding is that in the file narrative chlordiazepoxide treatment is rarely noted. The patients Erich H., Abdullah D., Hilde A., Erika B., and Karin A. were all treated with the drug, but this information appears only on an extra piece of paper stapled on to chart documentation or on the list of drugs in the discharge summary. Chlordiazepoxide is not mentioned in either the documentation for the clinical progression or in the list of therapeutic measures used in the epicrisis. It could be that the therapeutic intervention simply followed automatically and did not require a written deliberation process. This seems unlikely though, considering that chlordiazepoxide was used with such irregularity and among a significantly heterogeneous patient group. We can contrast the patient cases where chlordiazepoxide were and were not used; however, we cannot rule out a form of ‘‘tacit knowledge,’’ that is a ruling, but not documented knowledge.77 An analysis of the individual treatment courses confirms a dominating narrative in the search for a specific treatment diagnosis within the context of the Leonhard neurosis classification scheme. For the actor Stefan S. for example, who only spent three days after Christmas in the clinic, there is the following information: ‘‘In his utterances, a certain fearfulness and restlessness was always appearing, which was also at times superimposed with demonstrative traits [. . .]. After beginning a treatment with chlordiazepoxide, 3x1 pill daily, and with several psychotherapeutic talks, his mood improved somewhat, but not significantly. Due to the holidays and the short time available, a further clarification, especially of the internal findings, was unfortunately not possible.’’78 Here, with necessary haste, chlordiazepoxide was used to treat the patient’s ‘‘fearfulness’’ and ‘‘restlessness,’’ without diagnostic classification. This

remained, however, a core interest for the senior physician who wrote: ‘‘[. . .] I incline ever more to understand the witnessed occurrence as a reactive illness of a labile personality structure with strong accentuation [. . .]. I would be grateful if you would, in the frame of your capabilities, inform me as to your decision in this case, as well as your impression as a physician of Mr. S., as this would be of great interest to me both from a medical and from a scientific standpoint.’’79 Records belonging to the patients Hilde A. and Erika B. clearly demonstrate the use of chlordiazepoxide as a sleeping pill. ‘‘To resolve the sleep disturbances we gave 2 Timosin [chlordiazepoxide] at night,’’80 reads the file of the patient who was being treated for marital conflict. Erika B. came to the clinic with ‘‘frequent headaches’’81 and was then finally treated for a ‘‘paranoiac development of organic origin.’’82 ‘‘The patient would like to have Timosin again, as it helped her quite a lot,’’ reads the file.83 Four days later Erika B. received ‘‘2 tablets of Timosin in the evening’’ which continued for the last twelve days of her stay in the clinic.84 This is a clear case in which chlordiazepoxide is used without reference to any other treatment. We cannot assume that insomnia was a specific characteristic of this patient’s particular illness. The documentation demonstrates the patient’s desire for chlordiazepoxide—a desire that seems not only to have been accommodated, but also to have been the chief motivation for it being administered to her. The decision to use a tranquilizer as therapy was never discussed. Finally the case of Karin A., serves as an example for the use of the drug as a ‘‘last resort.’’ After a long previous treatment without the administration of psychotropic substances she was treated with Chlordiazepoxide for 145 days. The drug was administered apart from several changes in treatment diagnosis.85 To sum up our results we assert that chlordiazepoxide was indeed used in the Charité—especially in cases where previous treatment attempts had failed. The occasional demand, as well as the general acceptance of the drug on the part of the patients, demonstrated that the drug offered a compromise for achieving a successful symptomatic treatment. Psychiatrists and patients alike found that chlordiazepoxide met pragmatic and short-term needs, such as ‘‘calming’’ and ‘‘inducing sleep.’’86 But was there any attempt to standardize the application with regard to Leonhard’s diagnostics? In the case of chlordiazepoxide there was no conceptualization of how the drug could be used in a diagnostic-therapeutic practice. Clinical practice remained focused on the application of finely differentiated diagnostics, based on long-term observation and interviews. This diagnostic classification was not, however, able to develop a structural power regarding the therapeutic use of chlordiazepoxide. There was no significant shifting of diagnostic categories within the local context of this clinic as a response to the drug. Finally the use of the drug within the clinic varied significantly. In the psychotherapeutic wards, for example, chlordiazepoxide was not used at all—an indication that in this system of knowledge, pharmaceutical therapies were perceived as disruptive to the psychotherapeutical process. Therefore, systematisation of these

75 The classification in groups of diagnosis followed the ICD-6 code, documented at the clinic along with the classification of Leonhard. For quantitative analysis of Chlordiazepoxide, this system is merely helpful, because most individuals had a distinct diagnostic code. Ironically, the Charité system resisted common standardisation practices, and this occurs even today. 76 A review of all available drugs for ‘‘sedation’’ underscores this trend: 44 of 91 patients were treated with a sedative, but not one of them was hospitalized on ward 5. All drugs were examined that included the following ingredients: benzodiazepines, meprobamate, barbiturates, opiates, chloralhydrate, other formulas for ‘‘sleeping-pills’’ (e.g. ‘‘Benedorm’’, ‘‘Elrodorm’’ and herbals). 77 This is, however, part of the discussion about a selective representation of ‘‘reality’’ in sources for ‘‘everyday history’’. 78 PUB, PF 550/68. 79 PUB, PF 550/68, letter 15.4.1971. 80 PUB, PF 537/68, Epicrisis 10.2.1969. 81 PUB, PF 590/68, check list 28.10.1968. 82 PUB, PF 590/68, Epicrisis 11.12.1968. 83 PUB, PF 590/68, progress report 11.11.1968. 84 PUB, PF 590/68, Epicrisis 11.12.1968. 85 PUB, PF 169/68, progress report 18.4.1968. 86 These findings are of particular interest concerning the contemporary discourse on addiction to psychotropic drugs. The context, however, cannot be discussed here.

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pharmaceutical therapies was of little use. In this sense we can speak of a resistance to the translation of clinical practice into the Leonhardian standardisation strategy—this is what probably led to Leonhard’s relatively consistent rejection of chlordiazepoxide. Certainly it contributed significantly to the fact that no efforts were made to publish standardized evaluations of drug efficacy. The pragmatic considerations of other doctors, however, did lead to a certain level of chlordiazepoxide use. Leonhard and his scholars’ attempted to create their own efficacy assessment and seem to have been ambivalent about putting it into practice. Providing an overview of the standardisation research, we close our analysis with remarks on the rank of the Charité research in the scientific discourse of the time. 8. To draw the bow: standardisation of psychopharmaceuticals in psychiatry Across the entire GDR, debates in the 1960s were marked by discussions of reliable methods for evaluating psycho-pharmaceuticals. First however we consider the on-going international discussion that formed a critical reference for GDR psychiatrists. In order to put psycho-pharmaceuticals into use in a standardized manner, clinicians were decreasing their use of a nosology oriented toward disease entities. By the end of the 1950s, in the journal Der Nervenarzt [The Psychiatrist] the U.S. psychiatrist, Fritz Freyhan, suggested that the use of psycho-pharmaceuticals should be based on target symptoms. As Freyhan put it: It is therefore also useless to want to connect the therapeutic indications with clinical diagnoses [. . .]. For clinical evaluations it thus requires a double bookkeeping system, that apart from the diagnoses also describes the ‘‘target symptoms,’’ the modification of which is the purpose of the therapy. Only on the basis of collected data can psycho-pharmaceutical modes of effectiveness be differentiated between and can the results of examinations be compared in the literature.87 Although Freyhan’s method diametrically opposed the ideas of Schulze and other followers of the Leonhard school of thought, his ideas were extremely influential in the 1960s. Internationally the results of psycho-pharmaceutical therapy varied from clinic to clinic. In the Federal Republic of Germany as well, psychiatrists were occupied with unifying the varying results of psycho-pharmaceutical therapy from several clinics. To facilitate a more extensive exchange on psycho-pharmaceutical therapy, and in particular its standardisation, a network called the Working Group for Neuropsychopharmacology (Arbeitsgemeinschaft für Neuropsychopharmakologie (AGNP)) was established in the Federal Republic at the end of the 1950s. Five young psychiatrists in this group attempted to summarize the effectiveness of psycho-pharmaceuticals, based only on symptoms.88 Similar to the situation in the U.S., in the Federal Republic during the 1950s and 1960s the number of diagnostic schools made communication difficult.89 Additionally few psychiatrists believed that the new drugs worked specifically on entire dis-

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ease entities. At the same time, many researchers in the Federal Republic were bound to a phenomenological nosology that opposed splintering target symptoms. However, despite resistance, the five young psychiatrists did succeed in convincing most of the clinicians in the Federal Republic that a symptom-oriented evaluation of psychotropic action, shared by all clinicians, would be helpful to compare the differing results. In order to unify documentation practice they developed a diagnostic card that was to be appended to the front of every patient file. The five psychiatrists believed that the clinicians would be better able to standardize psycho-pharmaceutical therapy once they used the new documentation system in their clinical practice. At the end of the 1960s these cards were published as the AMP-System and used throughout the Federal Republic.90 In the GDR as well, these attempts at a ‘‘target symptom’’ orientation were influential. The director of the university psychiatric hospital in Halle, Helmut Rennert, along with his colleague GertEberhard Kühne, made a name for themselves with the development of a system of syndromatic, ‘‘psychiatric research fundamentals’’.91 Rennert, together with Karl Leonhard, was one of the most influential psychopathologists of the time. His basic idea was in opposition to Leonhard’s particular classification scheme. Rennert criticized other approaches, for example Leonhard’s, as placing too much emphasis on the pathogenetic aspect of an individual´s disease. Rennert’s ideas were based an Einheitspsychose—the belief that various forms of psychoses could be understood as nothing more than stages of the same process of illness development. Rennert and Kühne tried to employ psycho-pharmaceutical examinations as a tool to dissolve the ‘‘inconsistent, nosological conceptual frame’’ in new substance testing. According to the two, ‘‘the diagnosis was much less oriented on the disease as a whole as on the symptoms, which are characterized above all by the driving and affective model of agitation’’.92 The work produced at the Charité was initially a clearly identifiable reference point for the discourse of this problem. Kühne received Neumann and Schulze’s publications on imipramine, however, he questioned the validity of their evidence for the postulated therapeutic differentiation of depression.93 In a 1965 article, Kühne spoke of the chance for an ‘‘advance in understanding for nosology’’ by means of the psycho-pharmaceutical theory, but said that it still needed further development and while and an advance could be made ‘‘perhaps on the basis of Leonhard’s categorization’’ it would have to be with a more flexible separation of disease entities.94 Kühne formulated that this research approach was necessary, since at a minimum, there was a need for statistical investigation and evaluation. In the 1960s the research group performed psychopharmacological interventions on the basis of symptomrelated classifications determined in the efficacy studies for the ‘‘differential indications’’ of drugs.95 In 1971 Rennert wrote: To say it again in different words: as much as we admire the clinically minute Leonhardian syndrome description and at time also make use of it, for basic research it seems to us insignificant, whether a patient suffers for example from a ‘pure melancholy’ or from a ‘distrustful melancholy’ (all characterizations accord-

Freyhan (1957, p. 504). The five psychiatrists were Hanns Hippius, Dieter Bente, Kurt Heinrich, Max P. Engelmeier, Walter Schmitt. The German classification system of the time, the Würzburger Schlüssel, only separated diseases into broad categories. This allowed for a statistical overview of psychiatric disorders but did not include a scheme for pathopsychological differentiation on the basis of clinically significant symptoms. In practice, many psychiatrists complained that each clinic had to use its own classification schema. Kurt Schneider’s phenomenological approach stood in opposition to other physiological-phenomenological schools, such as that of Klaus Conrad (1905–1961) or the more anthropological school of the Frankfurt Ordinarius Jürg Zutt (1893–1980), the Swiss Binswanger school or the more hereditary-biologically oriented Berlin school. For an overview see Balz (2010, p. 409–419) and Balz & Hess (2009, p. 269–271). 90 For the detailed development of the documentation system cf. Balz (2010). For a deeper look at evaluation attempts in the history of the AGNP (Balz, 2008, p. 335–337). 91 Kühne & Rennert (1965, p. 140). 92 Kühne & Rennert (1965, p. 145). 93 Kühne (1965, p. 328). 94 Kühne (1965, p. 328). 95 Berrios & Beer (1994, p. 35) and Neumärker (2008, p. 330). 88 89

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ing to Leonhard); apart from all these labels, first and foremost we would register the relation (Petrilowitsch).96 Kühne and Rennert published an additional series of studies in which they continued to develop their nosology on the basis of psycho-pharmacological effectiveness tests. However, Rennert, as well as Leonhard and his scholars, felt obliged to further develop psychopathology and the publications of groups collaborating with Leonhard and Rennert determined the discussions of the 1960s in the GDR. However, by the 1970s the connection between psychopathology and psycho-pharmaceutical therapy was already tenuous and Leonhard and Rennert were regarded as a symbol of an antiquated, anti-therapeutic school. By the end of the 1960s, Ehrig Lange, a professor in Dresden, summarized a critique brought forward by reformers, in his report to the Problemkommission Medizin, [Problem Committee Medicine] a committee established by the Ministry of Health97: No diagnosis of a psychosis justifies the fixed supposition of a doomed course resulting in a fatalistic approach regarding the treatment options. Only the unfortunate individual case at the end of long efforts should show us whether the patient is a therapy-quitter or is non-suggestible. One should look at first for the cause of these phenomena in the therapeutic measures and their conditions, and, only in a final step, consider the problematic inherent laws of the disease itself.98 In the report, Lange explicitly criticized professors, like Leonhard and Rennert, and their main interest in the further development of psychopathology. Instead, he spoke out for a psychiatric discipline that left more room for recording therapeutic efforts. At the start of the standardized compilation of pharmaceutical efficacy, Lange had been willing to break new ground. As early as the mid1950s, Lange and his students had published numerous articles on psycho-pharmaceuticals, which were increasingly symptom-oriented.99 At the end of the 1960s, the Central Advisory Committee at the Ministry of Health finally asked the Dresden clinic to make a judgement regarding the need to import new psycho-pharmaceuticals.100 The Charité was also interested in testing the effectiveness of psycho-pharmaceuticals, like Haloperidol, which were not yet in use in the GDR, as described in correspondence between Leonhard and Lange.101 The fact that the Dresden Clinic, and not the Charité, received the award for testing is, as we see it, an indication of the increasing marginalisation of the Charité in psycho-pharmaceutical research.102 Lange and his colleagues made it clear, in their first publications on Haloperidol and Triperidol, that they judged the effectiveness of the psycho-pharmaceuticals on the basis of how they influenced the defined target symptoms drawing on publications of the West-German authors of the AMP-System.103 At the start of the 1970s Lange and colleagues composed an article calling for a new orientation in the psycho-pharmaceutical ther96

apy of the GDR. As the Dresden researchers argued, a new form of understanding of effectiveness must be employed to solve problems connected with the measurability and the specification of psychiatric phenomena as well as the quantification of various forms of [clinical] courses; since a process according to the old traditional method of subjective-descriptive understanding of psychiatric disorders without the possibility of statistically analyzable comparison is, in the future with the testing of psycho-pharmaceuticals as well, no longer viable.104 The authors called for a standardized system of documentation with target symptoms that could be evaluated electronically. They used the AMP-System developed by West German psychiatrists and advised other clinicians to do the same.105 Further discussions on the standardized evaluation of psychiatric drugs demonstrated that the debate focused on the electronic processing of data, which in effect created profiles that could be statistically analyzed.106 In states of the Eastern Block also, statistical and symptom-oriented evaluations were finally in the forefront. The famous Czech psychopharmacologist, Oldrich Vinar, summarized the conflict between the school advocating the old psychopathology-oriented approach of efficacy assessment and those favouring a symptom-oriented evaluation in his comment at the GDR-wide conference on psychotropic therapy in May 1972. He said: ‘‘Basically our approach is to avoid nosological-diagnostic considerations because we do not label the criteria for the patients’ sample as diagnostics. We use temporary provocative names like chlorpromazine affin or Aminitryptilin affin psychosis. If in doing so we will find groups of diseases with a common pathogenesis in the end, we might come to nosological diagnoses again.’’ 107 The Berlin psychiatrists no longer took part in the discussions about the adequate evaluation of efficacy of psychotropic drugs and seem to have lost their interest in psycho-pharmaceutical research. The final example was in 1970, the year of Leonhard’s retirement, when Schulze’s work on neuro-psycho-pharmaceutical therapy culminated in his own summary and definition of the problem of the fundamental disagreement regarding ‘‘symptom oriented or disease oriented psycho-pharmaceutical therapy.’’108 Against the background of the knowledge documented in the patient files, these papers allow for no doubt: the conflict, grown out of the attempt to integrate the newly available medicines into the system of clinical research practice, was not to be resolved. 9. Conclusion In this article we investigated the standardisation of the efficacy of psychopharmaceuticals in the Charité Psychiatric Clinic in the GDR. First, we described the administration of substances in the psychiatric clinic and subsequent translation in the Leonhard clinical system as a code of practice. Second, we illustrated the extent of the use of Leonhard’s model for a system of standardisation within

Rennert (1971, p. 410f). In this, the Ministry of Health Committee clinicians discusses developmental constraints in specific medical fields. They were divided in different sub-groups. The chair of the psychiatric sub-group was Ehrig Lange. 98 MFG (27.11.1967), pp. 7–8. 99 U.a. Lange (1955), Lange et al. (1966), Lange & Roßner (1966) and König (1967). 100 MFG (27.06.1968) and Schulze (1970). 101 ‘‘If it is possible, we would be very interested to participate in the testing of Triperidol and Haloperidol or one of both preparations.’’ HU (24.11.1965). 102 Presumably it was not only Lange’s consensus-viable form of standardising, but more importantly his influential position in the committee for psychiatry that was responsible. 103 Lange & Scholz (1968, p. 205, S. 266). Both publications were multi-center studies, which apart from the Dresden Clinic, the Jena Clinic and the Bezirkskrankenhaus in Görden were involved. The Jena clinicians mentioned that they judge the effectiveness of the psycho-pharmaceuticals on the basis of their influence on target symptoms. 104 König et al. (1971). 105 König et al. (1971). The comments of a group of GDR psychiatrists involved in the evaluation of psychotropic drugs expressed at a national conference in 1972 demonstrate that this demand was successful. In a first report on their research, the psychiatrists clarified that they based their efforts of standardisation on the AMP-system and the research by the Czech psychiatrist Oldrich Vinar (Blosfeld et.al. 1975, S. 119). 106 König (1972). Also to consider in this context are the other contributions in the journal Psychiatrie/Neurologie (cf. Dörre, 1972; Knöpfel, 1972; Papperitz, 1972). 107 Vinar (1975, S. 116). Vinar was the executive of the research institute for psychiatry in Prague (CSSR). 108 Schulze (1969, 1970). 97

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the clinic and how it resulted in a standardized form of drug evaluation. Third, we investigated the acceptance in the GDR, as a whole, of Leonhard’s approach as an instrument for standardisation. As we described at the end of the article, in the beginning of the 1960s Leonhard’s standardisation model was still accepted but ultimately could not establish itself as an instrument for the GDR as a whole. Was the failure of the local Leonhard standardisation model caused by the influence of Western-oriented models and their acceptance in the GDR? Or did the translation of drug effects in a paradigm of efficacy oriented to the psychopathology of Leonhard fail because of inherent contradictions? Reconstructing Schulze’s attempt to describe the use of imipramine as a standardized application within the coordinate system of the Leonhard research paradigm reveals resistance in practice. There was a gap between the documented practice in the patient files and the published casuistics. The treatment cases had to be significantly reconfigured in their narration to allow for translation into the idiosyncratic system of standardized use recommendations. In the case of chlordiazepoxide, initially there was no such attempt at a translation between the meaning inscribed in the practice and scientific publication. The use of chlordiazepoxide followed pragmatic implications, such as use as a sleeping pill, a somewhat rapidly available effect in short term treatments or as a last resort when previous therapies had failed. The fundamental assumptions of the Leonhard research program at the Charité could—both for himself and for his colleagues who were active in this field—only be brought into accord with the meanings constituted in the uses of the drugs with difficulty. In other words, the translation strategy, which is a necessary first step in the process of standardisation, failed. Though the doctors at the Charité claimed in the first half of the 1960s to have established their own model of standardisation, translation in clinical practice failed. The second step of clinical standardisation—the standardized use of Leonhard’s psychopathological approach—did not succeed. When one studies the clinical documentation in the patient files it was obviously not possible to develop a standardized administration of psychopharmaceuticals using Leonhard’s model. As we have shown, the influence of the ward structures, the personal preferences of the doctors, situational factors and presumably not in the least, and the complicated structure of Leonhard’s pathology were decisive in the

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failure of the translation. This resulted in a comparatively low level of productivity in this field of research. Nevertheless, psychiatric pharmaceutical-therapy became a significant field of interest for the discourse of GDR psychiatry specialists. Until the end of the 1960s, as well as many years later, it was still not possible for a researcher at the Charité psychiatric clinic to establish him/herself in this field. The rivalry in the field of psychopharmacological research, led to the marginalisation of the Berlin researchers compared to the university departments of Halle and Dresden. In the beginning of the 1960s it was still possible for university psychiatrists, like Leonhard, to shape the debate as they were regarded as indispensable researchers. At the end of the 1960s, GDR psychiatrists saw themselves confronted by a discussion dominated by a symptom-oriented standardisation. This leads to the conclusion that Störfreimachung was only partially successful in allowing the GDR to become independent from capitalist influences, although the GDR’s pharmaceutical industry was able to liberate itself from the expensive imports from the West to an extent. Also, in the case of the psychotropic drugs we examined, the reverse-engineering of pharmaceuticals was primarily carried out depending on medical necessities. The effects of the psychotropic drugs were documented according to these standardized symptom-oriented criteria first established in the West and later in the East. Indeed, there is no direct influence of representatives from the pharmaceutical industry in the process of standardizing efficacy in the GDR. However, the adoption of the models of evaluation established in the West illustrates that the GDR did not succeed in pursuing independent development in this field. Acknowledgement We thank Ulrike Klöppel for supplying us, in a very generous way, with results of her own archival research. Thanks to her research we were able to include the archival holdings of the VEB Arzneimittelwerke Dresden (AWD) and parts of the holdings of the Bundesarchiv Berlin (especially DQ1, Nr. 20905; DQ1 Nr. 3352) in this article. Additionally, we thank Volker Hess, Toine Pieters and Stephen Snelders for many helpful comments and Brigit Ramsingh for the proof-reading of the English text version.

Fig. A. The classification of endogenous psychoses by Leonhard (2003).

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Appendix See Appendix Figs. A–D.

Fig. B. Diagnoses in treatments with Imipramine in 1962.

Fig. C. Cases of treatment with Chlordiazepoxide, according to ward and diagnosis.

Fig. D. Days of treatment with Chlordiazepoxide, according to patients and wards.

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Archival material Archives of the Humboldt-University Berlin: Administrative files of the Charité psychiatric clinic HU (07.10.1958) Klara Iranyi an Karl Leonhard: Protokoll LSD-Selbstversuch (Nr. 038011/6). HU (o.A., 02/1962) Ahrens: Protokoll der Dienstbesprechung der Verbindungsärzte, Versorgungsausschuss der Charité am 21.02.1961 (Nr. 039012/4). HU (16.10.1961) Ahrens: Einladung zu einer außerordentlichen Sitzung der Verbindungsärzte der Kliniken zum Thema Störfreimachung bei der Arzneimittelversorgung (Nr. 039012/4). HU (o.A.,10/1961) Ahrens: Mit Anmerkungen versehenes und überarbeitetes Protokoll der außerordentlichen Dienstbesprechung der Verbindungsärzte, Versorgungsausschuss der Charité am 31.10.1961 (Nr. 039012/4). HU (17.05.1962) Karl Leonhard an Oguz Arkonac: Behandlung unterschiedlicher Psychoseformen (Nr. 038011/6). HU (o.A., 09/1962) Ahrens: Protokoll der Dienstbesprechung der Verbindungsärzte, Versorgungsausschuss der Charité, am 18.09.1962 (Nr. 039012/4). HU (o.A. 08/1963) Ahrens: Protokoll der Dienstbesprechung der Verbindungsärzte, Versorgungsausschuss der Charité am 20.08.1963 (Nr. 039012/4). HU (24.11.1965) Leonhard an Lange: Import von Quiloflex, Ospolot, Triperidol/ Haloperidol (Nr. 038011/6). HU (2.6.1966) Karl Leonhards an Dr. K. Hecht: Teilnahme Tagung CINP (Nr. 038011/ 6).

Archives of the Institute for the History of Medicine Berlin IGM (01.07.1963): Fotopolus/Leonhard: Planungsvorschlag 1964 (Perspektivplane 1959–1970).

Bundesarchive Berlin, Department GRD: Files of the Ministry of Health/ Ministerium für Gesundheitswesen (MfG) MFG (22.03.1962) Müller-Hegemann: Marsilid (DQ1 Nr. 20905). MFG (27.02.1963) Ahrens: Protokoll der Dienstbesprechung der Verbindungsärzte des Versorgungsausschusses der Charité am 19.02.1963 (DQ1 Nr. 3352). MFG (30.08.1963) Ahrens: Protokoll der Dienstbesprechung der Verbindungsärzte des Versorgungsausschusses der Charité am 20.08.1963 (DQ1 Nr. 3352). MFG (03.12.1961) Buthut:Bericht über die Beratung der Ärzte, Zahnärzte und Apotheker des Bezirkes Gera über die Arzneimittelversorgung am 02.12.1961 (DQ1 Nr. 3352). MFG (18.4.1963) Carstens: Bericht über Themenkatalog des Arbeitskreises ‘Synthetische Heilmittel’ (DQ1 Nr. 3352). MFG (o.A., 01/1956) Anonymous: Protokoll der 1. ordentlichen Sitzung des Zentralen Gutachterausschusses für Arzneimittelverkehr am 12.01.1956 (DQ1 Nr. 5781). MFG (27.11.1967) Lange: Aus der Problemkommission ‘‘Psychiatrie und Neurologie’’ des Rates für Planung und Koordinierung der medizinischen Wissenschaften beim Ministerium für Gesundheitswesen der DDR (DQ109 Nr. 258). MFG (27.06.1968) Lange an Kraatz: Projektentwürfe und Forschungsschwerpunkte (DQ 109 Nr. 258).

Saxony Economy Archive, Leipzig: Files of the Arzneimittelwerke Dresden (AWD) AWD (10.03.1964) Barth u.a.: Maßnahmeplan auf der Grundlage einer Auswertung einer Dienstreise zu einem Symposium über Tranquilizer in Wroclaw am 7. 9.11.1963 (Nr. 75).

Psychiatric Clinic, Charité, Berlin: Patient files (PUB, PF) All treatment cases from the years 1962 and 1968, especially: PUB, PF 664/62. PUB, PF 550/68. PUB, PF 537/68. PUB, PF 590/68. PUB, PF 169/68.

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