Between 1985 and 2024, Hungary's annual suicide rate gradually decreased from approximately 46 per 100000 people to approximately 17 per 100 000 people (i.e., by approximately 63 percent), while the number of patients receiving medication for depression increased twelvefold. Studies confirm that more widespread and effective treatment of depression has played a key role in this significant decline in suicides. There have been two periods of stagnation in the decline in suicide rates over the last 40 years: the first was between 2007 and 2011, while the second has been ongoing since 2019. These two periods were characterized by suboptimal functioning of psychiatric care and reduced access to care. Keywords: Hungary; suicide rate; suicide; antidepressants.

Bevezetés: A major depresszív zavar és a bipoláris zavar a betegek szempontjából jelentős életminőség-romlással, míg – gyakoriságuk miatt – össztársadalmi szinten komoly financiális terhekkel jár együtt. Tudomásunk szerint hazánkban, a teljes populációban, korábban még nem vizsgálták az e kórképek miatt az államilag finanszírozott ellátórendszerben kezelt betegek számát (az ún. „adminisztratív prevalenciát”), illetve – ebből következően – azt sem, hogy hogyan aránylik ez a korábbi, standardizált kérdőívekkel végzett, populációs mintákban talált valós gyakoriságokhoz, vagyis az ún. „epidemiológiai prevalenciához”. Célkitűzés: A major depresszív zavar, illetve a bipoláris zavar egyéves adminisztratívprevalencia-értékeinek becslése. Módszer: A Nemzeti Affektív Betegségek Regiszterében rögzített – a Nemzeti Egészségbiztosítási Alapkezelőtől (NEAK) származó – adatok elemzésével, kétféle kritériumrendszer (amelyeket „megengedő”, illetve „restriktív” protokollnak neveztünk el) használatával, a közfinanszírozott ellátórendszerben major depresszív zavar/bipoláris zavar miatti megjelenések és/vagy az e kórképek kezelésében használatos, ártámogatott gyógyszerek vénykiváltása alapján azonosított személyek számának meghatározása a 2024-es évre vonatkozóan, majd az adminisztratívprevalencia-értékek kiszámolása. Eredmények: A major depresszív zavar egyéves adminisztratív prevalenciáját, a „megengedő”, illetve a „restriktív” protokollt használva, a felnőtt korú népességben 2,12%-nak (férfiak: 1,26%; nők: 2,90%), illetve 1,70%-nak (férfiak: 0,98%; nők: 2,35%) találtuk. A bipoláris zavar vonatkozásában ugyanezek az értékek a következők voltak: 0,71% (férfiak: 0,55%; nők: 0,85%), illetve 0,60% (férfiak: 0,46%; nők: 0,73%). Megbeszélés: Vizsgálatunkban a hazánkban működő egészségbiztosítási alap, azaz a NEAK adatait feldolgozva becsültük meg a major depresszív zavar, illetve a bipoláris zavar egyéves adminisztratívprevalencia-értékeit. Ezeket a két kórkép egyéves epidemiológiai prevalenciájával összehasonlítva egyértelműen látszik, hogy mindkét betegség aluldiagnosztizált és/vagy alulkezelt hazánkban. Következtetés: A súlyos hangulatzavarban szenvedő betegeknek csupán cca. egynegyede jelenik meg a közfinanszírozott ellátórendszerben. Vizsgálatunknak számos limitációja van, amelyek csökkenthetik az adminisztratív prevalenciára vonatkozó becsléseink pontosságát. Orv Hetil. 2026; 167(4): 137–147.

Attention-deficit/hyperactivity disorder (ADHD) persists into adulthood in up to 60% of cases, affecting 2.5-6.8% of adults worldwide, with high comorbidity rates of mood, anxiety, and substance use disorders, and significant functional impairments, such as reduced quality of life, increased mortality, and economic burden. This review synthesizes etiological factors, including neuroimaging evidence of fronto-striatal and default mode network disruptions, high heritability up to 70-80% driven by common, polygenic and rare variants, and environmental risk factors. Treatment emphasizes multimodal approaches, with stimulants as first-line pharmacotherapy due to their superior efficacy over non-stimulants like atomoxetine and viloxazine. Novel agents in development, such as centanafadine triple reuptake inhibitor and solriamfetol target core symptoms and comorbidities, showing promising phase III results. Despite the high effect sizes of pharmacological treatment for ADHD, obstacles such as acceptance and adherence remain challenging. Neuromodulatory interventions, including transcranial direct current stimulation (tDCS) and neurofeedback, demonstrate moderate effects on inattention and executive function. Psychotherapeutic options, particularly cognitive-behavioral therapy (CBT)-based interventions, improve symptom management and emotional regulation, often as adjuncts to medication. The review highlights the need for personalized strategies addressing adherence, comorbidity, and long-term outcomes, emphasizing integrated care to mitigate ADHD's lifelong impact.

INTRODUCTION:Major depressive and bipolar disorder cause deterioration in the quality of life for patients and, due to their prevalence, result in serious financial losses at the societal level. To our knowledge, the number of patients treated for these disorders in the state-funded Hungarian healthcare system (the so-called "administrative prevalence") has not yet been examined at the level of the entire population. As a result, no study has yet been conducted to determine how the administrative prevalence compares to the true prevalence established in previous epidemiological studies using standardized questionnaires and population samples (i.e., the so-called "epidemiological prevalence"). OBJECTIVE:Estimating the 12-month administrative prevalence values for major depressive disorder and bipolar disorder. METHOD:Using data from the National Affective Disorders Register - sourced from the National Health Insurance Fund (NEAK) - and two sets of criteria (namely, "permissive" and "restrictive" protocols) to determine the number of individuals identified on the basis of their appearance in the publicly funded healthcare system and/or the dispensing of subsidized medicines used to treat major depressive disorder/bipolar disorder in 2024, and then calculating the administrative prevalence rates. RESULTS:Using the "permissive" and "restrictive" protocols, we found the one-year administrative prevalences of major depressive disorder to be 2.12% (male: 1.26%; female: 2.90%) and 1.70% (male: 0.98%; female: 2.35%), respectively. For bipolar disorder, the same figures were 0.71% (male: 0.55%; female: 0.85%) and 0.60% (male: 0.46%; female: 0.73%). DISCUSSION:Based on data from NEAK, we determined the 12-month administrative prevalence values for major depressive disorder and bipolar disorder. Comparing these with the annual epidemiological prevalences of the two disorders, it is clear that both conditions are underdiagnosed and/or undertreated in Hungary. CONCLUSION:Only about a quarter of patients with severe mood disorders appear in the publicly funded healthcare system. Our study has several limitations that may reduce the accuracy of our administrative prevalence estimates. Orv Hetil. 2026; 167(4): 137-147.

It is relatively common for patients suffering from major depressive disorder to experience no significant improvement in their depressive symptoms despite trying several antidepressants and/or other treatment methods. This phenomenon is referred to in the scientific literature and clinical jargon as "treatment-resistant depression" (TRD). In our review paper, we attempt to present various definitions of TRD and conceptually related categories (e.g., "therapy-refractory depression"; "difficult-to-treat depression") and to discuss the risk factors, differential diagnosis, and treatment options for TRD. Among the therapeutic options used in the treatment of TRD, we focus on the theoretical and practical aspects of the use of esketamine nasal spray, which has been available in Hungary for several years. The section discussing the practical aspects of esketamine use is based not only on the literature but also on the long-term experience gained by the staff of the esketamine treatment center at the Semmelweis University Department of Psychiatry and Psycho therapy with a large patient population. Keywords: treatment-resistant depression; major depressive disorder; antidepressant; esketamine; treatment.

Background: Patients with major depressive disorder (MDD) hospitalized for psychiatric emergencies (PE) represent a high-risk population, requiring immediate intervention. Overall survival and healthcare resource utilization were evaluated among MDD patients with PE (MDD-PE) vs without PE (MDD-nonPE) using data from the Hungarian National Health Insurance Fund database (2009 to 2020). Methods: Patients with MDD were selected if they had at least (i) 2 records of MDD diagnosis, or (ii) 1 record of MDD diagnosis and 1 prescription of antidepressant within 90 days of each other between 01 January 2010 and 31 December 2020. MDD-PE patients should have an inpatient hospitalization in a psychiatric ward dedicated for acute treatment, and/or a visit to an emergency department with >= 1 psychiatric and/or suicidal condition among the discharge diagnoses. Patients in the MDD-PE and MDD-nonPE cohorts were matched using a 1:1 propensity score matching algorithm based on age, gender, location of residence, and selected pre-index comorbidities. Results: 28,988 MDD-PE and 28,988 MDD-nonPE patients were included after propensity score matching. Overall survival was significantly shorter among MDD-PE vs matched MDD-nonPE patients (HR: 1.40, 95%CI: 1.33-1.48; p < 0.001). MDD-PE (vs matched MDD-nonPE) patients had significantly higher mean all-cause inpatient admissions (3.9 vs 1.4, p < 0.001) per patient per year (PPPY), and MDD-related inpatient admissions (2.3 vs 0.7, p < 0.001) PPPY with more days in hospital PPPY (all-cause: 65.4 vs 17.4 days; MDD-related: 25.9 vs 8.7 days). Conclusions: Findings emphasize the need for comprehensive care prioritizing increased vigilance for suicide risk and appropriate follow-up post-discharge among MDD-PE patients.

A tanulmány a magyarországi öngyilkossági halálozás 1955 és 2022 közötti alakulását vizsgálja a férfiak és a nők közötti abszolút és a relatív egyenlőtlenségek dinamikája alapján. A standardizált öngyilkossági ráták alapján bemutatjuk a nemek közötti különbségek időbeli változásait, köztük a gazdaságilag aktív és az időskorú férfiak és nők öngyilkossági szuicid viselkedésének tendenciáit. Az abszolút egyenlőtlenségek alapján két szakasz figyelhető meg, korcsoportoktól függetlenül. Az első, 1955 és 1985 közötti időszakban a különbségek meredeken növekedtek, majd ezt követően, a napjainkig is tartó periódusban meredeken csökkentek. A relatív egyenlőtlenségek kezdetben alacsonyak voltak, de az 1980-as évektől a férfi/nő arány markáns emelkedése volt megfigyelhető. Ez a szintváltás életkori bontás szerint eltérően jelentkezett: az idősebb korcsoportokban később következett be. A relatív egyenlőtlenségek időbeli mintázata jól közelíthető egy négyparaméteres logisztikus görbével. Az abszolút és a relatív mutatók alapján eltérő következtetések vonhatók le az öngyilkossági halandóság nemi egyenlőtlenségeiről. Míg a szakirodalom elsősorban a relatív különbségekre helyezi a hangsúlyt, addig jelen tanulmány az egyenlőtlenségek mindkét dimenziójának egyidejű bemutatását tartja szükségesnek.

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.

Abstract Background Major depressive disorder (MDD) is a leading cause of disability and premature mortality. This study compared the overall survival (OS) between patients with MDD and non-MDD controls stratified by gender, age, and comorbidities. Methods This nationwide population-based cohort study utilized longitudinal patient data (01/01/2010 – 12/31/2020) from the Hungarian National Health Insurance Fund database, which contains healthcare service data for the Hungarian population. Patients with MDD were selected and matched 1:1 to those without MDD using exact matching. The rates of conversion from MDD to bipolar disorder (BD) or schizophrenia were also investigated. Results Overall, 471,773 patients were included in each of the matched MDD and non-MDD groups. Patients with MDD had significantly worse OS than non-MDD controls (hazard ratio [HR] = 1.50; 95% CI: 1.48−1.51; males HR = 1.69, 95% CI: 1.66–1.72; females HR = 1.40, 95% CI: 1.38–1.42). The estimated life expectancy of patients with MDD was 7.8 and 6.0 years less than that of controls aged 20 and 45 years, respectively. Adjusted analyses based on the presence of baseline comorbidities also showed that patients with MDD had worse survival than non-MDD controls (adjusted HR = 1.29, 95% CI: 1.28–1.31). After 11 years of follow-up, the cumulative conversions from MDD to BD and schizophrenia were 6.8 and 3.4%, respectively. Converted patients had significantly worse OS than non-converted patients. Conclusions Compared with the non-MDD controls, a higher mortality rate in patients with MDD, especially in those with comorbidities and/or who have converted to BD or schizophrenia, suggests that early detection and personalized treatment of MDD may reduce the mortality in patients diagnosed with MDD.

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.

Depression is among the most common psychiatric illnesses, which imposes a major socioeconomic burden on patients, caregivers, and the public health system. Treatment with classical antidepressants (e.g. tricyclic antidepressants and selective serotonine reuptake inhibitors), which primarily affect monoaminergic systems has several limitations, such as delayed onset of action and moderate efficacy in a relatively large proportion of depressed patients. Furthermore, depression is highly heterogeneus, and its different subtypes, including post-partum depression, involve distinct neurobiology, warranting a differential approach to pharmacotherapy. Given these shortcomings, the need for novel antidepressants that are superior in efficacy and faster in onset of action is fully justified. The development and market introduction of rapid-acting antidepressants has accelerated in recent years. Some of these new antidepressants act through the GABAergic system. In this review, we discuss the discovery, efficacy, and limitations of treatment with classic antidepressants. We provide a detailed discussion of GABAergic neurotransmission, with a special focus on GABAA receptors, and possible explanations for the mood-enhancing effects of GABAergic medications (in particular neurosteroids acting at GABAA receptors), and ultimately, we present the most promising molecules belonging to this family which are currently used in clinical practice or are in late phases of clinical development.

Major mood disorder (i.e. major depressive disorder [MDD] and bipolar disorders [BPDs]) are among the most prevalent and disabling mental illnesses. Several, frequently intertwining theories (such as the monoamine, neuroinflammatory and neurotrophic theories) exist to explain the etiopathogenic background of mood disorders. A lesser-known hypothesis addresses the role of oxidative stress (OS; i.e. the overproduction and accumulation of free radicals) in the pathogenesis of these mental disorders. Free radicals are capable of damaging phospholipids, polyunsaturated fatty acids, proteins and nucleic acids. In the brain, OS impairs inter alia synaptic signalling and neuroplasticity. In the current paper, in addition to a brief description of the aforementioned pathophysiological processes involved in mood disorders (with a special focus on OS), we discuss in detail the results of studies on changes in non-enzymatic antioxidant uric acid (UA) levels in major mood disorders. Findings to date indicate that UA - a routinely measured laboratory parameter - may be a candidate biomarker to distinguish between MDD and BPD. Since the diagnostic criteria are identical for major depressive episodes regardless of whether the episode occurs in the context of MDD or BPD and also bearing in mind that the treatment for those two disorders is different, we may conclude that the identification of biomarkers to enable MDD to be distinguished from BPD would be of great clinical relevance. (Neuropsychopharmacol Hung 2024; 26(2): 105-124) Keywords: major depressive disorder, bipolar disorder, brain, oxidative stress, uric acid.

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.

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 cata-strophic 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.

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.

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.

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.

Abstract 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.