Lege Artis Medicinae

[Clozapine - the last resort antipsychotic for treatment resistant schizophrenia ]


JANUARY 20, 2020

Lege Artis Medicinae - 2020;30(01-02)

DOI: https://doi.org/10.33616/lam.30.007

[More than 60 years old is the first antipschychotic drug that is operating atypically as well. With its multifarious history it gained the golden standard title of all therapy resistent schisophrenic cases for the last three decades. In this article we place clozapine on the map of psychopharmacology and review its history’s most important chapters. In the third part we discuss some of the most relevant effects and side effects of clozapine in the light of latest research and practical considerations touching the problem of the optimal start timing. ]



Further articles in this publication

Lege Artis Medicinae

[End of the line? Addenda to the health and social care career of psychiatric patients living in Hungary’s asylums]


[The authors are focusing on a special type of long term psychiatric care taking place in Hungary outside of the conventional mental health care system, by introducing some institutional aspects of the not well known world of so called social homes for psychiatric patients (asylums). After reviewing several caracteristics of institutional development of psychiatric care in Hun­gary based on selected Hungarian and in­ternational historical sources, the main struc­tural data of present Hungarian institutional capacities of psychiatric health and social care services are shown. Finally, the authors based on own personal experiences describe several functional ascpects of the largest existing asylum in EU, a so­cial home for long term care of psychiatric pa­tients. By the beginning of the 20th century, Hungarian psychiatric institutions were operating on an infrastructure of three large mental hospitals standing alone and several psychiatric wards incorporated into hospitals. Nevertheless, at the very first session of the Psychiatrists’ Conference held in 1900 many professionals gave warning: mental institutions were overcrowded and the quality of care provided in psychiatric hospital wards, many of which located in the countryside of Hungary, in most cases was far from what would have been professionally acceptable. The solution was seen in the building of new independent mental hospitals and the introduction of a family nursing institution already established in Western Europe; only the latter measure was implemented in the first half of the 20th century but with great success. However, as a result of the socio-political-economic-ideological turn following the Second World War, the institution of family nursing was dismantled while different types of psychiatric care facilities were developed, such as institutionalised hospital and outpatient care. In the meantime, a new type of institution emerged in the 1950s: the social home for psychiatric pa­tients, which provided care for approximately the same number of chronic psychiatric patients nationwide as the number of functioning hospital beds for acute psychiatric patients. This have not changed significantly since, while so­cial homes for psychiatric patients are perhaps less visible to the professional and lay public nowadays, altough their operational conditions are deteriorating of late years. Data show, that for historical reasons the current sys­tem of inpatient psychiatric care is proportionately arranged between health care and social care institutions; each covering one third. Further research is needed to fully explore and understand the current challenges that the system of psychiatric care social- and health care institu­tions are facing. An in-depth analysis would significantly contribute to the comprehensive improvement of the quality of services and the quality of lives of patients, their relatives and the health- and social care professionals who support them. ]

Lege Artis Medicinae

["Punishment-therapy” - chances of psycho-rehabilitation for mentally ill offenders under forced medical treatment]


[When examining the life course of mentally disordered offenders it is unavoidable to take into consideration the legal definition of in­sanity that exempts an individual from ordinary punishment in the given context of criminal law. As technical as it is, legal language describes and prescribes institutional responses on how to deal with mentally disordered offenders - not being independent from the everyday societal stereotypes on mental illness. In Hungary, the definition of criminal liability consists of medical and legal elements. Thus, in practice court appointed psychiatric experts are solely relied upon in determining whether or not the accused are criminally liable - the formal decision is in the hands of the court. If no criminal liability is determined by the experts, the court has to acquit the accused. In some special cases this acquittal opens the way to criminal psychiatric detention that is maintained by the Hungarian Prison Service. The aims of criminal psychiatric detention are twofold: rehabilitation and punishment. We suggest that it is nearly impossible to serve both of the aforementioned aims simultaneously. Furthermore, our article argues that the philosophy of care is focused on punishment and biomedical treatment nowadays, rather than rehabilitation and holistic bio-psycho-social treatment. The approach of treatment in operation makes successful recovery of patient-detainees difficult. Moreover, there are systemic issues as well: limited effects of review proceedings, holes in the psychiatric-social institutional care system and the general societal stigmatisation of people with mental illnesses can unreasonably prolong discharging “guilty patients”, thus, they stay detained 4-5 years longer. ]

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[Meditation of the guest editor-in-chief]


Lege Artis Medicinae

[American-Hungarian forerunners of humanistic psychology and medicine: Andras Angyal and Bela Mittelmann ]


[The fact that there are two significant Hungarian pioneers in humanistic psycho­therapy is still not recognised in the Hungarian academic community. In order to redress this omission the author compares and considers the careers of András Angyal and Béla Mittelmann. Both individuals left Hungary in 1920, settling first in Europe and subsequently in America, where they separately enjoyed successful careers. According to the author the trajectory of their lives is quite representative of many Hungarian emigrants during this period in history. This study examines the course of their life and explores their main achievements in the context of their contemporary relevance and enduring legacies. In the case of Angyal, it is the holistic-organismic theory of personality and influence on Maslow, which are his paramount achievements. As regards Mittelmann his topical contribution has been to the practice of “coaching” on the one hand and the application of dance and body therapy to recovery on the other. ]

Lege Artis Medicinae

[The Veszprém model, alias a different approach of psychiatric care]


[This study describes an integration of a county-level psychiatric care unit with two elements of primary social care, namely the community psychiatric care and the daycare for psychiatric patients via mediation of a specific foundation. Adequate trainings make the connection and dual employment possible in the presented system. On the health care side development is characterized by extended psychiatric care with effective psychosocial interventions. Adding specialized group psychotherapies and sociotherapies to the activity of the social care also brought a quality change, extension of which provided self-help and the consumers' applicability as therapy leaders in sociotherapy group. Based on our ten years of practice we may declare that recovery-based psychiatric rehabilitation can be realized more effectively in this community-based biopsychosocial model of care. ]

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Clinical Neuroscience

TLR4 (Toll-like receptor-4) expression and frontal-cingulate volumes in schizophrenia

LI Hua, KÉRI Szabolcs

Evidence suggests that pathogen-associated pattern recognition receptors (Toll-like receptors, TLRs) are implicated in the pathophysiology of schizophrenia. TLRs are important in both peripheral immune responses and neuronal plasticity. However, the relationship between peripheral TLR expression and regional brain volumes is unknown in schizophrenia. We therefore assessed 30 drug-naïve, first-episode patients with schizophrenia. TLR4+/TLR1+ monocytes were measured using flow-cytometry. High resolution magnetic resonance images (T1 MRI) were obtained and analyzed with FreeSurfer. Results revealed significant negative correlations between the percentage of TLR4+ monocytes, mean fluorescent intensities, and brain volumes in frontal and anterior cingulate regions. The measures of TLR1+ monocytes did not show significant relationships with regional brain volumes. These results raise the possibility that abnormal TLR-activation is associated with decreased brain volumes in schizophrenia.

Clinical Neuroscience

Symptom profiles and parental bonding in homicidal versus non-violent male schizophrenia patients

HALMAI Tamás, TÉNYI Tamás, GONDA Xénia

Objective - To compare the intensity and the profile of psychotic symptoms and the characteristics of parental bonding of male schizophrenia patients with a history of homicide and those without a history of violent behaviour. Clinical question - We hypothesized more intense psychotic symptoms, especially positive symptoms as signs of a more severe psychopathology in the background of homicidal behaviour. We also hypothesized a more negatively perceived pattern (less Care more Overprotection) of parental bonding in the case of homicidal schizophrenia patients than in non-violent patients and non-violent healthy controls. Method and subjects - Symptom severity and symptom profiles were assessed with the Positive and Negative Syndrome Scale in a group of male schizophrenia patients (n=22) with the history of committed or attempted homicide, and another group (n=19) of male schizophrenia patients without a history of violent behaviour. Care- and Overprotection were assessed using the Parental Bonding Instrument (PBI) in a third group of non-violent healthy controls (n=20), too. Results - Positive, negative and general psychopathology symptoms in the homicidal schizophrenia group were significantly (p<0.005) more severe than in the non-violent schizophrenia group. Non-violent schizophrenia patients scored lower on Care and higher on Overprotection than violent patients and healthy controls. Homicidal schizophrenia patients showed a pattern similar to the one in the healthy control group. Conclusions - It seems imperative to register intense positive psychotic symptoms as predictive markers for later violent behaviour. In the subgroup of male homicidal schizophrenia patients negatively experienced parental bonding does not appear to be major contributing factor to later homicidal behaviour.

Clinical Neuroscience

[Relationship between the efficacy of atypical antipsychotics and polymorphism of dopamine D3 receptor in schizophrenia]

SZEKERES György, JUHÁSZ Anna, KÉRI Szabolcs, RIMANÓCZY Ágnes, SZENDI István, SZABÓ Zoltán, JANKA Zoltán

[Object - Numerous relevant variants of dopamine receptors have been identified in schizophrenia. The Ser9Gly gene polymorphism of dopamine D3 receptor is known as a susceptibility factor for the disease. In addition, it has a role in the modification of therapeutic effect of antipsychotics. In this naturalistic study the authors investigated the relationship between this polymorphism and the therapeutic response to atypical antipsychotics. Method - 75 patients with schizophrenia according to DSM-IV and 45 healthy controlls were recruited. The patients were divided to responder and nonresponder subgroups, cut-off: >20 point improvement in Global Assessment of Functioning. By polymerase chain reaction the genotype of dopamine D3 receptor of every participant was determined. Results - The Ser9Ser genotype of dopamine D3 receptor was more frequent in the nonresponder subgroup (64%, p=0.0018). The Ser9 allele was overrepresented among nonresponder patients (82%, p=0.0172). Conclusion - Based on our results, the worse therapeutic response to atypical antipsychotics is associated with Ser9 variant of dopamine D3 receptor.]

Lege Artis Medicinae



[As many as 80% of patients with schizophrenia have serious problems with the compliance at some point during their course of their treatment. In most cases, patients are partially compliant, taking only a portion of their prescribed medication. Early warning signs of such partial compliance may confuse some clinicians with non-response to treatment and may result in switching these patients to alternative oral antipsychotic drugs. This review focuses on factors that can contribute to partial compliance such as poor insight, negative attitude or subjective response toward medication, cognitive dysfunction, treatment-related side effects, substance abuse and complicated treatment regimen. Partial compliance is among the most common causes of psychotic relapse and the need for rehospitalisation. The reduced incidence of adverse side effects such as extrapyramidal symptoms with atypical antipsychotic agents has the potential to improve compliance in the maintenance treatment of schizophrenia. Administration of a long-acting injectable antipsychotic provides confirmation of whether patients have taken their medication. Furthermore, it allows physicians to distinguish non-response and non-compliance. Strategies for managing partial compliance include the use of a long-acting injectable atypical antipsychotic, psychoeducation and cognitive-behavioural interventions.]

Clinical Neuroscience

[Event-related potentials and clinical symptoms in schizophrenia]


[The investigation of schizophrenia’s aetiology and pathomechanism is of high importance in neurosciences. In the recent decades, analyzing event-related potentials have proven to be useful to reveal the neuropsychological dysfunctions in schizophrenia. Even the very early stages of auditory stimulus processing are impaired in this disorder; this might contribute to the experience of auditory hallucinations. The present review summarizes the recent literature on the relationship between auditory hallucinations and event-related potentials. Due to the dysfunction of early auditory sensory processing, patients with schizophrenia are not able to locate the source of stimuli and to allocate their attention appropriately. These deficits might lead to auditory hallucinations and problems with daily functioning. Studies involving high risk groups may provide tools for screening and early interventions; thus improving the prognosis of schizophrenia. ]