Volume 11, Issue 4, December 2009
Editoral in Hungarian
Gábor Faludi
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Klasszifikáció, molekuláris pszichiátria és terápia….
A klinikai gyógyszervizsgálatok heterogén populációban történnek szkizofréniában, a réginek mondott nomenklatúra szerint például hebefrén, paranoid, kataton, vagy szisztémás, nem-szisztémás kórformákat vizsgálnak együtt, vagy ún. study populációkat vonnak be, és utána nem értjük, vajon miért van jelentős mértékű placebo válasz. Ugyanez a helyzet a depresszió kutatásban, klinikailag nyilvánvalóan különálló fenotípusokat kezelnek egy szerrel, és az arra adott terápiás válaszkészséget értékelik, például a paranoid depressziót a vitalisan lehangolt, érzelmileg nem rezonábilis formával és/vagy az iteratív panaszkodó-szorongó, szegényes tematikájú depressziót a hipochondriás formával vetik össze, majd bonyolult statisztikákkal értékelik a sok esetben szerény farmakológiai válaszokat.A pszichotrop hatást a pszichiátriai betegségben a szer agyi struktúrákon kifejtett hatásmódja szerint értékelik. A jelenlegi neuropszichofarmakológiai kutatások részben az előbb említettek miatt pusztán a nemkívánatos hatások terén adnak releváns visszajelzést a gyártók felé, mivel a pszichotrop szerek hatását farmakológiailag heterogén populáción vizsgálják.
A mai gyógyszermarketing célja, hogy a pszichotrop szereket minél szélesebb populációban értékesíthessék, ezért az oktatás egyik fő feladata az lenne, hogy megértesse, ne használják a pszichiátriai szereket válogatás nélkül minden esetben.
Az oktatás leválasztása a marketingről, a pszichés zavarok terápiás válaszkészséget mutató formáinak identifikálása és a pszichotrop szerek terápiás profiljának felvázolása egy új klasszifikációs módszer, az „Összetett Diagnosztikai Kiértékelő Rendszer” (CODE) segítségével válhat lehetővé. A famakológiailag valid pszichiátriai nozológia fejlesztése alapul szolgálhat annak a módszertannak kidolgozásához, melyet ún. nozológiai homotípusokon alapuló „nozológiai mátrixnak” nevezünk.
A nozológiai homotípusok a mentális betegségek elemi egységei, és a nozológiai mátrixban olyan pozíciót töltenek be, mint a nozológiai organizációs alapelvek: 1. totalitás 2. lefolyás és kimenetel 3. polaritás. A nozológiai homotípusok tehát homogénebb populációt jelölnek ki, mint a jelenlegi diagnosztikai rendszerekkel azonosítható bármely betegpopuláció. A pszichotropok az agyi szignáltranszdukcióra és a kórkép lefolyására gyakorolt hatásuk alapján definiálhatók, melyek molekuláris genetikai és agyi képalkotó vizsgálatokkal kiegészülve és a nozológiai mátrix alkalmazásával klinikai eredményekké alakíthatók.
A pszichofarmakológiai kutatásokban és a racionális farmakoterápiában új perspektíva nyílhat egy Összetett Diagnosztikai Kiértékelő Rendszer és a nozológiai mátrix használatával, alkalmazásukkal relevánsabb klinikai visszajelzéseket kapna a gyógyszeripar, így lehetővé válna, hogy szelektívebb és személyre szabottabb szereket fejlesszenek ki a mentális betegségek gyógyítására.
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Although the possibilities of antidepressive pharmacotherapy are continuously improving, the rate of nonresponders or partial responders is still relatively high. Suicidal behavior, the most tragic consequence of untreated or unsuccessfully treated depression, commonly develops in the first few weeks of antidepressive treatment before the onset of therapeutic action and is strongly related to certain specific symptoms of depression like insomnia.
The present paper reviews the newly discovered and well-documented antidepressive effect of quetiapine in bipolar and unipolar depression with special regards to its early onset of action, and its sleep-improving effects. Both beneficial effects play an important role in the reduction of suicidal risk frequently seen in depressed patients.
Keywords: mirtazapine, major depression, insomnia, suicide, side-effects
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Due primarily to developments in immunology, chemotherapy and hygiene the estimated life expectancy at birth increased during the last century from about 55 years to 80 years.
Since the human Technical Life Span (TLSh) is about 120 years and life expectancy is today steadily increasing by about 2.2 months/year, a life span of 100 years may appear quite soon. Knoll developed (-)-deprenyl, the first anti-aging drug, the prophylactic administration of which increased significantly the average life span of animals. (-)-Deprenyl became a world-wide used experimental tool as the first selective inhibitor of B-type MAO and being the unique MAO inhibitor free of the cheese effect was introduced to treat Parkinson’s disease, because it could be administered in combination with levodopa without side effects. However, Knoll demonstrated in his later work that (-)-deprenyl has enhancing qualities already in femto-picomolar concentrations, which leave MAO-B activity unchanged, and the activity of the catecholaminergic neurons in the brain stem and this previously unknown ‘enhancer effect’ is responsible for the peculiar therapeutic benefits caused by (-)-deprenyl. Knoll proposed 25 years ago to slow the aging of the brain, the decay of behavioral performance, prolong life, and prevent or delay the onset of age-related neurodegenerative diseases such as Parkinson’s and Alzheimer’s via the prophylactic daily administration of 1 mg (-)-deprenyl. At present (-)-deprenyl belongs to the best known anti-aging drugs and a rapidly growing number of people are already trying to slow the aging of their brain by taking (-)-deprenyl as a prophylactic agent.
Nevertheless, up to the present, an exact analysis with placebo control of the capacity of (-)-deprenyl to prevent or delay the onset of neurodegenerative diseases is still missing. It is already very much on the map to perform such a study with this world-wide highly esteemed Hungarian drug.
Keywords: (-)-deprenyl, enhancer regulation, anti-aging effect, prophylactic therapy
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Introduction: Disturbances of perception play a considerable role in depressed patients’ symptoms. These symptoms are mostly secondary in the daily practice, however, the disturbances of perception of a mild degree lead to cognitive distortions, and they make the recognition of the depression significantly more difficult. Purpose: To review several systems of diagnostic criteria, five developed in Europe, ten in the area of the United Kingdom, five in the United States and five other diagnostic systems with respect to the kind of significance they ascribe to the disturbances of perception in the presence of the depression. Results: The author establishes that the diagnostic systems examined in case of the patients suffering from depression ascribe different significances to the disturbances of perception despite the fact that all depressed patients suffer from these symptoms. In case of the 23 examined disturbances of perception, out of the 25 systems 20 ascribe significance to fewer than ten symptoms, 11 systems ascribe significance to five or fewer symptoms. In the process of the simplification of the diagnostic systems these symptoms do not obtain emphasis, which makes the establishment of the accurate diagnosis difficult. The author emphasizes that in the background of disturbances of perception the detection of the misshapen reality hides, from which the patients suffer the most. Out of the examined diagnostic systems the European and the complex diagnostic systems ascribe a more considerable emphasis to the disturbances of perception. In Kielholz’s system there are 14, while in the CODE system there are 19 kinds of disturbances of perception. Conclusion: The author establishes that the disturbances of perception and the symptoms developed by the consequences of the disturbances of perception have a greater significance in patients suffering from depressive disorders than it is known in the common knowledge. In fact most of the psychiatric signs and symptoms may be attributable to some kind of disturbance of perception. Out of the examined diagnostic systems Paul Kielholz’s and Thomas Ban’s complex diagnostic system, the CODE-DD takes the significance of the disturbances of perception into consideration in the largest degree. It is necessary to keep in mind that patients suffering from depression with disturbances of perception also present have difficulty in recovery. In the process of the simplification of the diagnostic systems these symptoms may evade the doctors’ attention making the recognition of the illness more difficult and weaken the efficiency of the therapy. It would be justified to indicate the disturbances of perception as a diagnostic criterion in the ICD-11 and in the DSM-V among the illnesses related to depression. Paying attention to the disturbances of perception may transform the system of psychiatric classifications and the research of psychiatric illnesses not only in case of affective disorders but also in case of psychoses. Especially the genetic research concerning the disturbances of perception may support the objective judgement of the psychiatric disorders, its biological tenability could stabilize the situation of psychiatry among medical sciences.
Keywords: disturbance of perception, symptoms, signs, depressive disorders, diagnostic systems.
The role of childhood abuse in adult suicidal behaviour
Annamária Rihmer, Simon Szilágyi, Sándor Rózsa, Xénia Gonda, Gábor Faludi and Zoltán Rihmer
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In our present study we have analysed the influence of childhood abuse on affective temperament-types and Gotland Male Depression Scale scores in 150 nonviolent suicide attempters. Our findings confirm previous Hungarian and international data concerning the connection of suicidal behaviour and psychiatric disorders, undesirable psychosocial circumstances and negative life events. Moreover, our study provides new results regarding the strong association of the affective temperament types, male type of depression, seriously traumatic early life events and furthermore their predisposing role in connection with suicidal behaviour. Suicide attempters, experiencing physical and/or sexual abuse in their childhood showed significantly higher total scores (p<0.05) on cyclothymic and irritable temperament subscales. The Gotland Male Depressive syndrome was equally very common and equally serious both in males and females who made a nonviolent suicide attempt. However, regardless of gender, it was significantly more severe (p<0.01) among those who were victims of both physical and sexual childhood abuse.
Keywords: affective temperament-types, childhood abuse, Gotland Male Depression
Scale, suicide attempt
Early experiences with Suboxone maintenance therapy in Hungary
Zsolt Demetrovics, Judit Farkas, Jozsef Csorba, Attila Nemeth, Barbara Mervo, Janos Szemelyacz, Eniko Fleischmann, Akos Kassai-Farkas, Zsolt Petke, Tibor Orojan, Sandor Rozsa, Peter Rigo, Sandor Funk, Mate Kapitany, Anna Kollar, Jozsef Racz
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Background: Suboxone (Buprenorphine/naloxone) is a novel drug used in opiate substitution therapy. In Hungary, it was introduced in November 2007. Suboxone is a product for sublingual administration containing the partial μ-receptor agonist buprenorphine and antagonist naloxone in a 4:1 ratio. Objective: Objectives of our study were to monitor and evaluate the effects of Suboxone treatment. Method: 6 outpatient centers participated in the study, ; 3 from Budapest and 3 from smaller cities in Hungary. At these centers, all patients entering Suboxone maintenance therapy between November 2007 and March 2008, altogether 80 persons (55 males, 35 females, mean age = 30,2 years, SD=5,48) were included in the study sample. During the 6-month period of treatment, data were collected 4 times; when entering treatment, 1 month, 3 months, and 6 months after entering treatment. Applied measures were the Addiction Severity Index, SCID-I, SCID-II, Hamilton Depression Scale, Hamilton Anxiety Scale, STAI-S State Anxiety Inventory, Beck Depression Inventory, Heroin Craving Questionnaire, WHO Well-being Inventory, Perceived Stress Scale, ADHD retrospective questionnaire, TCI short version, and Ways of Coping questionnaire. Results: Nearly fourth of the altogether 80 heroin dependent patients (18 persons, 22.5%) dropped out of treatment during the first month (the majority, 12 persons [15%] during the first week) or chose methadone substitution instead. Following this period however, dropout rate decreased and the six-month treatment period was completed by 32 patients (40%). During the first month of treatment significant positive changes were experienced in all studied psychological and behavioral dimensions that proved to be stabile throughout the studied period. Conclusions: According to the early experience with Suboxone treatment, it is a well tolerable and successfully applicable drug in the substitution therapy of opiate addicts. A critical phase seems to be the first one or two weeks of treatment. Dropout rate is high during this early period, while after a successful conversion clients presumably remain in therapy for a long period. At the beginning of administration special emphasis must be put on informing patients, especially concerning withdrawal symptoms that might be present during the first week, which highly contributes to better retention in treatment.
Keywords: Suboxone, buprenorphine, naloxone, heroin substitution, maintenance therapy, effectiveness, Hungary
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Antipsychotics have been used in the therapy of schizophrenia and bipolar disorder and several second generation antipsychotics (SGA) are already available in Hungary. The clinical trials’ results are confusing in regarding the differences in the efficacy of the SGA’s, but the differences in their side-effects are clear. Considering its most important side-effects, such as extrapyramidal symptoms, weight gain, metabolic syndrome and prolactin level elevation, quetiapine has a fairly good side effect profile, and can therefore be recommended especially in case of bipolar patients who are highly sensitive towards side effects.. In our case-report, we present four patients who were succesfully treated with quetiapine for their psychotic mood elevation.
Keywords: quetiapine, psychosis, mood-elevation