Settling a distracted globe: An overview of psychosocial and psychotherapeutic treatment of attention-deficit/hyperactivity disorder.

While the currently prevailing theory of ADHD postulates a neurobiological background and core deficits of behavioural inhibition and executive functioning as the basis of ADHD symptoms, our current conceptualisation also acknowledges the essential contributory role of psychosocial, ecological, and cognitive factors. Considering the multifactorial background of ADHD, its treatment equally needs to be multifactorial involving, besides pharmacotherapy, skill development and psychotherapy as well, especially if we postulate the increasing contribution of social factors in the background of the increasing burden of ADHD. Pharmacotherapies, including stimulants and non-stimulant ADHD medications applied as first-line treatments have a positive effect on core behavioural symptoms, however, they often do not sufficiently remediate several other symptoms and comorbid disorders, which are consequences of ADHD, especially considering that ADHD persists into adulthood and is present over the whole life span. Furthermore, pharmacological treatment is not sufficient to substitute for the skills needed to manage symptoms and adapt well to the environment. As part of a multimodal treatment approach, psychological therapies for ADHD target, besides core ADHD symptoms, other associated features including emotional dysregulation, personality development, neurocognitive dysfunction, depression, anxiety, and sleep problems. Insufficiently treated ADHD may contribute to psychological and personality developmental problems in children, as well as increased health costs and decreased productivity warranting multimodal treatment to address the areas not sufficiently targeted by ADHD-specific pharmacotherapy.

Recovering from the first shock? Changes in suicidality during the first two years of the COVID-19 pandemic in a country with traditionally high levels of completed suicides.

BACKGROUND: Hungary was among the few countries where suicidality increased in the first year of the COVID pandemic. In this study, we sought to investigate whether that elevated suicide mortality had changed by 2021, when the number of fatalities due to COVID-19 was much higher than in 2020. METHODS: We used an interrupted time-series analysis with (quasi-) Poisson regression, controlling for linear trend and seasonal effects, to estimate the effect of the pandemic on the suicide rates of various subpopulations. For both pandemic years the changes in risk of suicide were compared to the period between 2015 and 2019. RESULTS: Although the pandemic had a significant adverse effect on suicidality in 2020 in the Hungarian total population and in males, by 2021 this effect had vanished. In the total population, those aged 25 years and older had elevated suicidality in 2020 but neither age group in the total population had elevated suicidality in 2021. In the total population, increased risks of suicide death could be observed among residents of the capital city (in 2020 and 2021), villages (in 2020), and - in terms of regions - "Central Hungary" (in 2020 and 2021). Only the risk of violent suicides was significantly higher for both the total and male populations (and only in 2020). LIMITATIONS: We used non-individual level data. CONCLUSIONS: The increased suicidality in 2020 had abated by 2021. In the paper, we discuss the possible explanations for our findings.

[Fortification of drinking water with lithium to reduce suicide in the population].

Antimanic and phase-prophylactic features of lithium (Li) in subjects with affective disorders has been known for a long while. Furthermore, it has also been proven for decades that - partially due to its aforementioned effects - Li has marked antisuicide properties in subjects with mood disorders. Intriguingly, consistent findings from several studies conducted in the last 15 years suggest that the antisuicide effect of Li can also be detected in those members of the population who consume drinking water with high Li contents (in connection with this, we must note that the level of Li in tap water is several orders of magnitude less than the therapeutic dose of Li). Based on these results, and also taking into the consideration the long-known anti-goiter effect of iodized table salt, some experts suggest considering the enrichment of tap water with microdose Li. This paper paper briefly summarizes our current knowledge on this topic as well as the related clinical and ethical dilemmas.

Fight the Fire: Association of Cytokine Genomic Markers and Suicidal Behavior May Pave the Way for Future Therapies.

The fight against suicide is highly challenging as it may be one of the most complex and, at the same time, most threatening among all psychiatric phenomena. In spite of its huge impact, and despite advances in neurobiology research, understanding and predicting suicide remains a major challenge for both researchers and clinicians. To be able to identify those patients who are likely to engage in suicidal behaviors and identify suicide risk in a reliable and timely manner, we need more specific, novel biological and genetic markers/indicators to develop better screening and diagnostic methods, and in the next step to utilize these molecules as intervention targets. One such potential novel approach is offered by our increasing understanding of the involvement of neuroinflammation based on multiple observations of increased proinflammatory states underlying various psychiatric disorders, including suicidal behavior. The present paper overviews our existing understanding of the association between suicide and inflammation, including peripheral and central biomarkers, genetic and genomic markers, and our current knowledge of intervention in suicide risk using treatments influencing inflammation; also overviewing the next steps to be taken and obstacles to be overcome before we can utilize cytokines in the treatment of suicidal behavior.

How to save a life: From neurobiological underpinnings to psychopharmacotherapies in the prevention of suicide.

The impact of suicide on our societies, mental healthcare, and public health is beyond questionable. Every year approximately 700 000 lives are lost due to suicide around the world (WHO, 2021); more people die by suicide than by homicide and war. Although suicide is a key issue and reducing suicide mortality is a global imperative, suicide is a highly complex biopsychosocial phenomenon, and in spite of several suicidal models developed in recent years and a high number of suicide risk factors identified, we still have neither a sufficient understanding of underpinnings of suicide nor adequate management strategies to reduce its prevalence. The present paper first overviews the background of suicidal behavior including its epidemiology, age and gender correlations, and its association with neuropsychiatric disorders as well as its clinical assessment. Then we give an overview of the etiological background, including its biopsychosocial contexts, genetics and neurobiology. Based on the above, we then provide a critical overview of the currently available intervention options to manage and reduce risk of suicide, including psychotherapeutic modalities, traditional medication classes also providing an up-to-date overview on the antisuicidal effects of lithium, as well as novel molecules such as esketamine and emerging medications and further molecules in development. Finally we give a critical overview on our current knowledge on using neuromodulatory and biological therapies, such as ECT, rTMS, tDCS, and other options.

Suicide in Hungary during the first year of the COVID-19 pandemic: Subgroup investigations.

BACKGROUND: COVID-19 may unfavourably affect the mental health of individuals in various ways. Accordingly, the concern has been raised that national suicide rates will increase in the wake of the outbreak of the pandemic. METHODS: In the current study, we tested this conjecture in three age groups (<25; 25-64; ≥65) of the Hungarian total population and the male and female populations. In addition, we assessed whether the pandemic had different effects on counts of suicides committed by violent or non-violent methods. Finally, by comparing the monthly suicide rates in 2020 and the corresponding monthly rates in 2019, we also investigated the "pulling together" hypothesis that postulates that a temporary decrease in suicides may occur after large-scale catastrophic events. RESULTS: With regard to the total population only the suicide counts of individuals aged 25-64 rose significantly (p < 0.05) during the COVID months of 2020. Similar patterns, but at lower levels of significance (0.05 < p < 0.1), were found in those members of the total population aged 65 or older and among males aged between 25 and 64. Furthermore, we found that the number of violent suicides increased significantly (p < 0.05) during the COVID months. Finally, our results have not confirmed the existence of a "pulling together" phenomenon in association with the COVID-19 pandemic in Hungary. LIMITATIONS: We used non-individual level data and were therefore unable to control suicide risk factors at the level of individuals. DISCUSSION: The number of suicides rose significantly in some subgroups of the Hungarian population during the COVID months of 2020.

Novel antidepressant drugs: Beyond monoamine targets.

Treatment of major depressive disorder (MDD) including treatment-resistant depression (TRD) remains a major unmet need. Although there are several classes of dissimilar antidepressant drugs approved for MDD, the current drugs have either limited efficacy or are associated with undesirable side effects and withdrawal symptoms. The efficacy and side effects of antidepressant drugs are mainly attributed to their actions on different monoamine neurotransmitters (serotonin, norepinephrine, and dopamine). Development of new antidepressants with novel targets beyond the monoamine pathways may fill the unmet need in treatment of MDD and TRD. The recent approval of intranasal Esketamine (glutamatergic agent) in conjunction with an oral antidepressant for the treatment of adult TRD patients was the first step toward expanding beyond the monoamine targets. Several other glutamatergic (AXS-05, REL-1017, AV-101, SLS-002, AGN24175, and PCN-101) and GABAergic (brexanolone, zuranolone, and ganaxolone) drugs are currently in different stages of clinical development for MDD, TRD and other indications. The renaissance of psychedelic drugs and the emergence of preliminary positive clinical trial results with psilocybin, Ayahuasca, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD) may pave the way towards establishing this class of drugs as effective therapies for MDD, TRD and other neuropsychiatric disorders. Going beyond the monoamine targets appears to be an effective strategy to develop novel antidepressant drugs with superior efficacy, safety, and tolerability for the improved treatment of MDD and TRD.

[Suicide mortality in Hungary during the COVID-19 pandemic.] / Öngyilkossági halálozás Magyarországon a COVID­19-pandémia idején.

INTRODUCTION: While suicide rates did not change (or decreased) in the first pandemic year (i.e., 2020) in the majority of countries, in Hungary the number of completed suicides rose significantly. OBJECTIVE: In our study, we investigated whether the unfavourable trend reversal of the Hungarian suicide rate following the outbreak of COVID-19 pandemic persisted in the second pandemic year. METHOD: We used an interrupted time-series analysis with Prais-Winsten regression, controlling for time and seasonal effects as well as autoregressive effects, to estimate the effect of the pandemic on the suicide rates of the Hungarian male, female and total populations in 2020 and 2021. RESULTS: In the first pandemic year, we observed a significant increase in suicide rates in males and the total population. Although the case numbers for males and the total population in 2021 exceeded the case numbers of the pre-pandemic year, regression estimates suggest that the increase in rates did not differ significantly from the pre-pandemic years in males and it was only found to be significant at the 10% level in the total population. DISCUSSION AND CONCLUSION: Based on the examination of data from the first two pandemic years, we may conclude that by 2021 the adverse effect of the pandemic on suicidality reduced in the total population and disappeared in males. The question remains open whether this favourable development will continue. Orv Hetil. 2022; 163(48): 1895-1901.

Serotonin and depression - a riposte to Moncrieff et al. (2022).

In their recently published systematic "umbrella" review, Moncrieff and colleagues conclude that there is no consistent evidence that depression is caused by decreased serotonin activity in the central nervous system (CNS). However, this paper - which was extensively publicized and received a lot of attention on the social media - can cause misunderstandings, since the serotonin hypothesis of depression in its original form (i.e. reduced serotonin activity in the CNS = depression) formulated more than 50 years ago has been considered outdated for several decades. It has long been known that depression is a heterogeneous disorder not only genetically, clinically and biologically but also from a pharmacotherapeutic perspective. The decreased activity of serotonin, which undoubtedly plays an essential role in the pathogenesis of depression, is characteristic of only a subgroup of depressed subjects whose clinical picture is mostly dominated by intensified negative emotions, agitation, anxiety, insomnia, decreased appetite, self-blame and suicidality and these individuals are primarily responsive to SSRIs. By contrast, depression cases with reduced positive affects (characterized by anhedonia, anergia, inhibition and reduced cognitive functions) are mainly caused by a disturbance in the metabolism of dopamine and/or noradrenaline. These patients are primarily responsive to dual-action (e.g. SNRI) antidepressants. Results of serotonin and catecholamine (dopamine, noradrenaline) depletion studies also suggest that that the dysregulation of serotonin and dopamine/noradrenaline in the CNS is characteristic of different subgroups of depressed patients. In addition to the serotonergic, dopaminergic and noradrenergic systems, many other neurotransmitter systems (e.g. cholinergic, glutamatergic, GABAergic) and other mechanisms (e.g. neuroinfl ammation) have also been proven to play a role in the development of the disorder. Knowledge of the data presented in our publication is important since the simplistic interpretation by Moncrieffetal. of the role of serotonin in the pathogenesis of depression may undermine confidence in SSRIs in many patients. (Neuropsychopharmacol Hung 2022; 24(3): 120-125).

A bitter pill to swallow? Impact of affective temperaments on treatment adherence: a systematic review and meta-analysis.

BACKGROUND: Predominant affective temperament may affect adherence to prescribed pharmacotherapeutic interventions, warranting systematic review and meta-analysis. METHODS: The Scopus, Web of Science, PubMed, and OVID MedLine databases were inquired since inception up to 31st of March 2022 for records of any study design documenting quantitative evidence about affective temperaments as measured by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-A) questionnaire and treatment adherence measured by the means of major rating scales on the matter. People with low vs. high levels of treatment adherence, matched for otherwise clinically relevant variables, were deemed as cases and controls, respectively, using standardized mean differences (SMDs) in pertinent scores under random-effects meta-analysis. RESULTS: Nine studies encompassing 1138 subjects pointed towards significantly higher cyclothymic (SMD = -0.872; CI: [-1.51 to -0.24]; p = 0.007), irritable (SMD = -0.773; CI: [-1.17 to -0.37]; p < 0.001) and depressive (SMD = -0.758; CI: [-1.38 to -0.14]; p = 0.017) TEMPS-A scores both for psychiatric and nonpsychiatric samples with poorer adherence. LIMITATIONS: Intrinsic limitations of the present report include the heterogeneity of the operational definitions documented across different primary studies, which nonetheless reported on the sole medication-treatment adherence, thus limiting the generalizability of the present findings based on a handful of comparisons. CONCLUSIONS: Though further primary studies need to systematically account for different clinical and psychosocial moderators across different clinical populations and operational definitions, cyclothymic, depressive, and irritable temperament scores may nonetheless predict treatment adherence and, thus, overall treatment outcomes.

The relationship between therapeutic adherence and personality.

Inadequate adherence to long-term therapies significantly affects the course and outcome of the disease, and therefore poses a serious threat to both the effectiveness and success of treatment and the long-term well-being of patients. Therapeutic adherence is an extremely complex process, with a number of risk and protective factors identified, many of which underlie the psychological characteristics of the patient. A number of medication adherence models have been developed to take into account the psychological characteristics of patients, and recent research has examined the relationship between different personality models and adherence to therapeutic recommendations. In this review we aim to summarize current knowledge, adherence models, research findings on the relationship between personality and adherence, including implications for future research.

Change of Circulating Vascular Endothelial Growth Factor Level and Reduction of Anhedonia Are Associated in Patients With Major Depressive Disorder Treated With Repetitive Transcranial Magnetic Stimulation.

Aim: Vascular endothelial growth factor (VEGF) has been implicated in mediating the effect of antidepressant therapies as it plays a significant role in the neurogenesis. Anhedonia, an endophenotype of major depressive disorder (MDD), is related to the dorsolateral prefrontal cortex, the major focus of brain stimulation in MDD. The aim of our study was to analyze the change of serum VEGF level after rTMS treatment in association with anhedonia. Materials and Methods: A dataset of 17 patients with TRD who were treated with antidepressants and bilateral rTMS for 2 × 5 days was analyzed. Depression was measured by the Montgomery-Asberg Depression Scale (MADRS) and anhedonia by the Snaith-Hamilton Pleasure Scale (SHAPS) for monitoring the symptom changes. The serum VEGF levels and symptoms were assessed on the first (V1), on the 14th (V2), and on the 28th day (V3). The level of VEGF was measured by ELISA assay. Results: There was no significant association between MADRS scores and serum VEGF levels at any timepoint. The decrease in the SHAPS score was significantly associated with the increase in VEGF level between V1 and V2 (p = 0.001). The VEGF levels were significantly higher in non-responders than in responders (p = 0.04). The baseline VEGF level has been proven as a significant predictor of treatment response (p = 0.045). Conclusion: Our results suggest that serum VEGF can be sensitive to the changes of anhedonia during rTMS treatment. Considering that the most widely used depression scales are not applicable for the assessment of anhedonia, measurement of anhedonia in rTMS treatment studies of patients with TRD can be suggested as more appropriate data on distinct pathogenic pathways and specific biomarkers of the disorder.

Invisible wounds: Suturing the gap between the neurobiology, conventional and emerging therapies for posttraumatic stress disorder.

A sharp increase in the prevalence of neuropsychiatric disorders, including major depression, anxiety, substance use disorders and posttraumatic stress disorder (PTSD) has occurred due to the traumatic nature of the persisting COVID-19 global pandemic. PTSD is estimated to occur in up to 25% of individuals following exposure to acute or chronic trauma, and the pandemic has inflicted both forms of trauma on much of the population through both direct physiological attack as well as an inherent upheaval to our sense of safety. However, despite significant advances in our ability to define and apprehend the effects of traumatic events, the neurobiology and neuroanatomical circuitry of PTSD, one of the most severe consequences of traumatic exposure, remains poorly understood. Furthermore, the current psychotherapies or pharmacological options for treatment have limited efficacy, durability, and low adherence rates. Consequently, there is a great need to better understand the neurobiology and neuroanatomy of PTSD and develop novel therapies that extend beyond the current limited treatments. This review summarizes the neurobiological and neuroanatomical underpinnings of PTSD and discusses the conventional and emerging psychotherapies, pharmacological and combined psychopharmacological therapies, including the use of psychedelic-assisted psychotherapies and neuromodulatory interventions, for the improved treatment of PTSD and the potential for their wider applications in other neuropsychiatric disorders resulting from traumatic exposure.

Investigation of the association between lithium levels in drinking water and suicide mortality in Hungary.

BACKGROUND: In recent decades, a series of ecological studies from various countries have attempted to reveal whether there is an association between trace amounts of lithium in drinking water and suicide mortality. With some notable exceptions, results have indicated that there is an inverse association between these two variables. Since Hungary had extremely high rates of suicide with a persistent spatial pattern, we consider that our country is ideal to investigate this research question. METHODS: We carried out our research on Hungarian data at the level of districts (n = 197). The dependent variable was the age- and gender-standardized mortality ratio for suicide (sSMR). Our main explanatory variable was the tap water lithium level (Li) from public drinking water supply systems using their own water source (n = 1 325). Those data, which give full national coverage, were aggregated to the level of districts. Confounding factors were religiosity, alcohol consumption and income. Various regression models were used for statistical calculations. RESULTS: Findings from our most appropriate regression model - adjusted for relevant confounding variables and able to handle spatial autocorrelation and heteroscedasticity - suggest a significant (p < 0.05) and a trend-like (p < 0.1) negative association between Li and sSMR in the total population and among males, respectively. However, such an association was not found between these two variables among females. CONCLUSION: In line with the majority of findings from other countries, our results indicate that the intake of lithium with drinking water may have a gender-dependent suicide-protective effect.

Topological Dissection of Proteomic Changes Linked to the Limbic Stage of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause of dementia worldwide. In AD, neurodegeneration spreads throughout different areas of the central nervous system (CNS) in a gradual and predictable pattern, causing progressive memory decline and cognitive impairment. Deposition of neurofibrillary tangles (NFTs) in specific CNS regions correlates with the severity of AD and constitutes the basis for disease classification into different Braak stages (I-VI). Early clinical symptoms are typically associated with stages III-IV (i.e., limbic stages) when the involvement of the hippocampus begins. Histopathological changes in AD have been linked to brain proteome alterations, including aberrant posttranslational modifications (PTMs) such as the hyperphosphorylation of Tau. Most proteomic studies to date have focused on AD progression across different stages of the disease, by targeting one specific brain area at a time. However, in AD vulnerable regions, stage-specific proteomic alterations, including changes in PTM status occur in parallel and remain poorly characterized. Here, we conducted proteomic, phosphoproteomic, and acetylomic analyses of human postmortem tissue samples from AD (Braak stage III-IV, n=11) and control brains (n=12), covering all anatomical areas affected during the limbic stage of the disease (total hippocampus, CA1, entorhinal and perirhinal cortices). Overall, ~6000 proteins, ~9000 unique phosphopeptides and 221 acetylated peptides were accurately quantified across all tissues. Our results reveal significant proteome changes in AD brains compared to controls. Among others, we have observed the dysregulation of pathways related to the adaptive and innate immune responses, including several altered antimicrobial peptides (AMPs). Notably, some of these changes were restricted to specific anatomical areas, while others altered according to disease progression across the regions studied. Our data highlights the molecular heterogeneity of AD and the relevance of neuroinflammation as a major player in AD pathology. Data are available via ProteomeXchange with identifier PXD027173.

Changes in suicide mortality of Hungary during the first year of the COVID-19 pandemic / A magyarországi öngyilkossági halálozás változásai a COVID-19-járvány elso évében.

Összefoglaló. Bevezetés: Az öngyilkosság fo rizikófaktorának a pszichiátriai zavarokat tekintjük. A COVID-19 többek között neuropszichiátriai kórképek kialakulásához is vezethet. Ezen túl a pandémia egyéb velejárói, mint például az izoláció vagy a munkahelyvesztés, a társadalom egészséges tagjaiban is stresszhez, végül pszichiátriai zavarokhoz vezethetnek. Célkituzés: Vizsgálatunk célja annak a teóriának a tesztelése volt, hogy a fenti tényezok miatt együtt járt-e a járvány a hazai suicid halálozás csökkeno trendjének irányváltásával. Módszer: Vizsgálatunkban a megszakított idosorok elemzésének módszerét használtuk, a becslésekhez kvázi-Poisson-regressziót alkalmazva, hogy összehasonlítsuk a 2010 és 2020 közötti idoszak havi bontású adataiból kirajzolódó trendek alapján a járvány idoszakában (2020. március-december) "elvárt" öngyilkossági esetszámokat a ténylegesen bekövetkezett esetek számával. Eredmények: A COVID-19-hónapok alatt a férfiak által elkövetett öngyilkosságok száma szignifikánsan, 18%-kal nott, ahhoz a trendhez képest, amely a COVID-19 hiányában állt volna elo. A teljes populációban szintén szignifikáns, 16%-os emelkedést lehetett megfigyelni, míg a nok által elkövetett öngyilkosságok száma nem tért el szignifikánsan a pre-COVID-19-idoszak trendje alapján elvárt értéktol. Megbeszélés és következtetés: A járvány kitörése utáni idoszakban a magyar férfiak szignifikánsan gyakrabban követtek el öngyilkosságot, míg a noknél az adatok nem tükröztek lényegi változást. A más országokban kivitelezett vizsgálatok eredményei érdekes módon inkább csökkenést vagy nem szignifikáns változást jeleztek, amikor a COVID-19-éra suicid számait az azt megelozo idoszakok számaival hasonlították össze. A hazai és a nemzetközi eredmények közti eltérések magyarázata egyelore még nem ismert, így a téma mindenképpen további vizsgálatokat igényel. Orv Hetil. 2021; 162(41): 1631-1636. INTRODUCTION: Psychiatric disorders are the main risk factors for suicide. COVID-19 may result in the appearance of neuropsychiatric syndromes. Moreover, other corollaries of the pandemic (e.g., isolation, job loss) may lead to increasing stress and, ultimately, psychiatric disorders even among the non-infected population. OBJECTIVE: We aimed to test the theory of whether the pandemic, due to the aforementioned factors, was associated with the reversal of the declining suicide rate trend in Hungary. METHOD: To compare the observed number of suicides during the COVID-19 months (March-December 2020) with the expected numbers, we used an interrupted time series model and, for the estimations, quasi-Poisson regression. Expected numbers were calculated based on trends derived from monthly data between 2010 and 2020. RESULTS: During the months of the pandemic, the number of suicides among males rose significantly by 18% compared to the hypothetical trend that would have occurred in the absence of COVID-19. A significant increase (16%) was also observed in the total population. By contrast, the number of female suicides did not differ significantly from the number expected based on the pre-COVID-19 trend. DISCUSSION AND CONCLUSION: After the outbreak of the epidemic, Hungarian males committed significantly more suicides, while no relevant changes were observed among females. Interestingly, studies from other countries found either no change or decrease when comparing suicide numbers from the COVID-19 period with the corresponding numbers from the pre-COVID-19 period. The explanation for this discrepancy is still lacking, so further investigations are needed. Orv Hetil. 2021; 162(41): 1631-1636.

Statistics on completed suicides committed in Hungary in the period between 2000 and 2019 / A 2000 és 2019 közötti idoszakban Magyarországon elkövetett, befejezett öngyilkosságok statisztikai elemzése

Összefoglaló. Bevezetés: Az öngyilkosság régóta jelentos probléma hazánkban. Célkituzés: Az elmúlt 20 év során elkövetett, befejezett öngyilkosságok elemzése három idointervallumban (2000-2006, 2006-2010, 2010-2019) nemek, korcsoportok, az elkövetési mód, a családi állapot és a munkanélküliség szempontjából. További célunk volt a pszichiátriai ellátást negatívan érinto, 2007. évi egészségügyi reform suicid halálozással való összefüggéseinek vizsgálata. Módszer: A suicid halálozást a Központi Statisztikai Hivatal adatainak felhasználásával elemeztük. Az évenkénti suicid rátát 100 000 lakosra adtuk meg. Az adatok statisztikai feldolgozásához az Excel 2011-es, az SPSS 23-as és az amerikai NIH Jointpoint programjának 4.8.0.1-as verzióját használtuk. Eredmények: 2000 és 2019 között 51,4%-kal csökkent a suicid halálozás (nok: 15,57 vs. 7,69/100 000 fo; férfiak: 51,5 vs. 24,73/100 000 fo, összlakosság: 32,61 vs. 15,85/100 000 fo). A legnagyobb mértékben a férfiak és a középkorúak körében csökkent a mortalitási ráta, a legkevésbé a fiatal, egyedülálló noknél. A leggyakoribb elkövetési mód változatlanul az akasztás (58,4%). A 20 évig tartó rátacsökkenés 2006 után több évre megtorpant, és egészen 2010-ig nagyjából konstans maradt (24,43 vs. 24,88/100 000 fo). Azt feltételezzük, hogy ennek hátterében jelentos részben a pszichiátriai ellátórendszert negatívan érinto, 2007-ben bevezetett egészségügyi reform állt. Ez a megtörés kimutatható volt szinte minden korcsoportnál, a leggyakoribb elkövetési módoknál, és egyaránt érintette a hajadonokat/notleneket, a házasokat, az özvegyeket és az elváltakat. Csak 2010 után kezdodött újra a suicid mortalitás szignifikáns csökkenése. Az utolsó 10 év alatt 36,3%-kal csökkent a suicid mortalitás (24,88 vs. 15,85/100 000 fo), ami kiemelkedo eredmény az európai országok körében. Következtetés: Egy elhibázott, a pszichiátriai ellátórendszert sújtó egészségügyi reform következményeként az addig egyenletesen csökkeno suicid halálozás üteme 2006 után megtört, és néhány évig stagnált. Több évig tartott, mire bizonyos mértékig rendezodött a pszichiátriai ellátórendszer, és ennek köszönhetoen 2010 után ismét folyamatosan és szignifikánsan csökkent a suicid mortalitás. Orv Hetil. 2021; 162(32): 1283-1296. INTRODUCTION: In Hungary, suicide has been a major public health issue for a long time. OBJECTIVE: Our objective was to examine data on completed suicide cases in Hungary from a 20-year period divided into three intervals (2000-2006; 2006-2010; 2010-2019) grouped by sex, age, methods of commitment, marital and employment statuses. An auxiliary aim was to assess the associations between the healthcare reform in 2007 (with unfavourable impacts on the psychiatric care system) and suicide mortality. METHOD: Data on suicide were provided by the Hungarian Central Statistical Office. In all cases, the yearly suicide rates were given for 100 000 inhabitants. For statistical calculations, we used Excel 2011, SPSS v. 23 and NIH Joinpoint Regression Program v. 4.8.0.1. RESULTS: Between 2000 and 2019, there was a 51.4% reduction in the suicide mortality (females: 15.57 vs. 7.69/100 000; males: 51.5 vs. 24.73/100 000; total population: 32.61 vs. 15.85/100 000). The greatest declines occurred among males and middle-aged. At the same time, the rate of young single females declined only slightly. The most common method of commitment remained hanging (58.4%). During the 20-year-long period investigated, there was a temporary halt between 2006 (24.43/100 000) and 2010 (24.88/100 000) in the otherwise steadily declining trend of the rate. One of the major underlying causes of this plateau is presumed to be the healthcare reform commenced in 2007 with negative impacts on psychiatric services. This plateau was observable in almost all subpopulations irrespective of their age, marital status and the suicide method they used. The decline of the rate restarted only after 2010. In the last 10 years, suicide mortality has decreased by 36.3% (from 24.88 to 15.85/100 000) in Hungary, which is a very good result in a European comparison. CONCLUSION: Due to an unsound health reform threatening the psychiatric care, the previously experienced declining trend of the suicide rate halted in 2006 and has remained almost unchanged for a few years during which psychiatric services could be restored in some degree. From 2010, as a consequence of this restoration, the marked decline of the suicide rate restarted and has been remained stable. Orv Hetil. 2021; 162(32): 1283-1296.

A Real-World, Prospective, Multicenter, Single-Arm Observational Study of Duloxetine in Patients With Major Depressive Disorder or Generalized Anxiety Disorder.

Background: Suboptimal treatment response during anti-depressive treatment is fairly common with the first antidepressant (AD) choice, followed by switching to another agent in the majority of cases. However, the efficacy of this strategy over continuation of the original agent is less solidly documented in real-life studies. The aim of our present study was to ascertain the effects of switching to duloxetine following inadequate response to prior ADs on general illness severity, pain, and health-related quality of life in a large sample of major depressive disorder (MDD) and generalized anxiety disorder (GAD) patients in a prospective, real-world, multicenter, observational study. Methods: A total of 578 participants with MDD or GAD were enrolled in 58 outpatient sites in an 8-week, single-arm, open-label, flexible-dose trial with duloxetine. Severity of symptoms [with Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I)], severity of pain (with a Visual Analog Scale), satisfaction with current treatment, and health-related quality of life [with the three-level version of the EuroQol five-dimensional questionnaire (EQ-5D-3L)] measures were recorded at baseline and at follow-up visits 4 and 8 weeks after initiation of treatment. Data were analyzed using ANOVA and mixed linear models. Results: 565 patients completed the study and comprised the analyzed dataset. Results indicated that severity of illness significantly decreased over the 8 weeks of the study and already at 4 weeks in both patient groups. Overall quality of life and all of its subindicators also significantly improved in both patient groups and so did subjective experience of pain. Satisfaction with current treatment also significantly increased during the study period. Frequency of side effects was low. In both GAD and MDD groups, two patients dropped out of the study due to adverse effects, leading to treatment termination in four cases (0.7%). Conclusions: This 8-week, multicenter, flexible-dosing, single-arm, open-label, observational real-life study in MDD and GAD patients switched to duloxetine after inadequate response or low tolerability to other ADs showed a significant positive effect on all outcome measures, including a significant decrease in illness severity as well as significant overall symptomatic improvement, with good tolerability.

Clozapine Withdrawal-Induced Malignant Catatonia or Neuroleptic Malignant Syndrome: A Case Report and a Brief Review of the Literature.

ABSTRACT: In our brief literature review, we discuss the changes in the concept of catatonia as well as its various types and symptoms. We also succinctly review the possible symptoms of clozapine withdrawal. In addition, we analyze the main features of the very few published cases of clozapine withdrawal-induced catatonia and the relationship between neuroleptic malignant syndrome and the malignant subtype of catatonia. Furthermore, we present the case of a 29-year-old male patient with schizophrenia in whom a malignant catatonic episode/neuroleptic malignant syndrome (with negativism, stupor, mutism, autonomic signs [eg, fever, hyperhidrosis], and elevated creatine kinase levels) began 5 days after the patient decided arbitrarily to cease his clozapine treatment. His catatonic symptoms quickly (ie, within a few days) resolved after the reinstitution of clozapine. Finally, we attempt to provide a theoretical explanation for the surprising finding in the literature that the withdrawal of clozapine, unlike the withdrawal of any other antipsychotics, may be associated with catatonia (frequently its malignant subtype). The take-home message of our case is that clinicians should bear in mind the risk of catatonia (especially the malignant subtype of it) after the prompt withdrawal of clozapine therapy.