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Edema as an adverse drug reaction is a commonly underestimated yet potentially debilitating condition. This study analyzes the incidence of severe psychotropic drug-induced edema (e.g., edema affecting the face, legs, or multiple body parts and lasting for more than 1 week, or in any case necessitating subsequent diuretic use) among psychiatric inpatients. The cases under examination are derived from an observational pharmacovigilance program conducted in German-speaking countries ("Arzneimittelsicherheit in der Psychiatrie", AMSP) from 1993 to 2016. Among the 462,661 inpatients monitored, severe edema was reported in 231 cases, resulting in an incidence of 0.05%. Edema occurred more frequently in women (80% of all cases) and older patients (mean age 51.8 years). Pregabalin had the highest incidence of severe edema, affecting 1.46 of patients treated with pregabalin, followed by mirtazapine (0.8). The majority of edema cases showed a positive response to appropriate countermeasures, such as dose reduction and drug discontinuation, and resolved by the end of the observation period. While most instances of drug-induced edema are reversible, they can have a significant impact on patient well-being and potentially result in decreased treatment adherence. It is, therefore, crucial to remain vigilant regarding risk-increasing circumstances during treatment with psychotropic drugs.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Edema/induzido quimicamente , Edema/epidemiologia , Edema/tratamento farmacológico , Pregabalina , Psicotrópicos/efeitos adversos , FarmacovigilânciaRESUMO
INTRODUCTION: Vasopressin (AVP) and oxytocin (OT) exert sex-specific effects on social pair bonding and stress reactions while also influencing craving in substance use disorders. In this regard, intranasal oxytocin (OT) and AVP antagonists present potential treatments for tobacco use disorder (TUD). Since transcription of both hormones is also regulated by gene methylation, we hypothesized sex-specific changes in methylation levels of the AVP, OT, and OT receptor (OXTR) gene during nicotine withdrawal. METHODS: The study population consisted of 49 smokers (29 males, 20 females) and 51 healthy non-smokers (25 males, 26 females). Blood was drawn at day 1, day 7, and day 14 of smoking cessation. Craving was assessed with the questionnaire on smoking urges (QSU). RESULTS: Throughout cessation, mean methylation of the OT promoter gene increased in males and decreased in females. OXTR receptor methylation decreased in females, while in males it was significantly lower at day 7. Regarding the AVP promoter, mean methylation increased in males while there were no changes in females. Using mixed linear modeling, CpG position, time point, sex, and the interaction of time point and sex as well as time point, sex, and QSU had a significant fixed effect on OT and AVP gene methylation. The interaction effect suggests that sex, time point, and QSU are interrelated, meaning that, depending on the sex, methylation could be different at different time points and vice versa. There was no significant effect of QSU on mean OXTR methylation. DISCUSSION: We identified differences at specific CpGs between controls and smokers in OT and AVP and in overall methylation of the AVP gene. Furthermore, we found sex-specific changes in mean methylation levels of the mentioned genes throughout smoking cessation, underlining the relevance of sex in the OT and vasopressin system. This is the first study on epigenetic regulation of the OT promoter in TUD. Our results have implications for research on the utility of the AVP and OT system for treating substance craving. Future studies on both targets need to analyze their effect in the context of sex, social factors, and gene regulation.
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Ocitocina , Tabagismo , Masculino , Feminino , Humanos , Ocitocina/genética , Ocitocina/metabolismo , Receptores de Ocitocina/genética , Receptores de Ocitocina/metabolismo , Tabagismo/genética , Epigênese Genética , Vasopressinas/genética , Vasopressinas/metabolismo , Metilação , Arginina Vasopressina/genética , Receptores de Vasopressinas/genéticaRESUMO
OBJECTIVE: Most patients with alcohol use disorder (AUD) regularly take medication. Alcohol interacts negatively with many commonly prescribed medications. Little is known about whether the risk of potential alcohol-medication and drug-drug interactions increases or decreases in patients with AUD during inpatient withdrawal treatment. The aim of our study was to determine the prevalence and characteristics of potential alcohol-medication and drug-drug interactions in patients with AUD before and after withdrawal treatment in an addiction unit. DESIGN: Prospective monocentric quasi-experimental pre-post study. METHODS: Medication records before and after withdrawal treatment were analyzed and screened for potential alcohol-medication (pAMI) and drug-drug interactions (pDDI) using the drugs.com classification and the AiDKlinik® electronic interaction program, respectively. RESULTS: We enrolled 153 patients with AUD who were treated in an addiction unit of a university hospital in Germany. Of these, 67.3% experienced at least one pAMI before and 91.5% after withdrawal treatment. In total, there were 278 pAMIs classified as "mild," "moderate," or "severe" before and 370 pAMIs after withdrawal treatment. Additionally, there were 76 pDDIs classified as "moderate," "severe," or "contraindicated combinations" both before and after withdrawal treatment. CONCLUSION: The risk of exposure to pAMIs and pDDIs increases during inpatient withdrawal treatment in patients with AUD. Improvements in the quality of prescribing should particularly focus on the use of antihypertensives and opioids.
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Alcoolismo , Interações Medicamentosas , Pacientes Internados , Síndrome de Abstinência a Substâncias , Humanos , Masculino , Feminino , Alcoolismo/tratamento farmacológico , Pessoa de Meia-Idade , Adulto , Estudos Prospectivos , Alemanha , IdosoRESUMO
BACKGROUND: Approximately 15-25% of depressed patients suffer from difficult-to-treat depression (DTD). Patients with DTD require a thorough examination to avoid the oversight of treatable (psychiatric/somatic) comorbidities or (pseudo-)resistance to antidepressant drugs (ADs). Polymorphisms of the cytochrome P450 (CYP) enzymes 2D6 and 2C19, which play a major role in the metabolism of ADs, may contribute to resistance to ADs. Patients with DTD might benefit from electroconvulsive therapy (ECT). METHODS: We enrolled 109 patients with DTD and 29 untreated depressed controls (UDC). We assessed risk phenotypes, comorbidities, and treatment, including ECT. We also performed pharmacokinetic analyses of CYP2D6 and CYP2C19. RESULTS: DTD patients significantly more often suffered from comorbid psychiatric diseases, especially ICD-10: F40-F48 (DTD:40.4%, UDC:17.2%, OR 11.87, p=0.011) than UDC patients. DTD patients receiving ECT were more likely to achieve remission (37.7% vs. 11.8%, OR=3.96, p=0.023). Treatment with ADs did not differ between remitters and non-remitters. No significant differences were observed in the distribution of CYP2D6 and CYP2C19 variants between both groups. CONCLUSION: Patients with DTD appear to experience comorbid neurotic stress and somatoform disorders (ICD-10: F40 - F48) more frequently. Therefore, a comprehensive differential diagnosis is crucial when patients do not respond sufficiently to antidepressant medication. Genotyping CYP2D6 and CYP2C19 should be considered.
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Antidepressivos , Comorbidade , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2D6 , Eletroconvulsoterapia , Fenótipo , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Antidepressivos/uso terapêutico , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2C19/genética , Idoso , Adulto , Transtorno Depressivo Resistente a Tratamento/terapia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/genética , Estudos de Coortes , Resultado do TratamentoRESUMO
BACKGROUND: Prader-Willi syndrome (PWS) is commonly associated with intellectual disability, but also with a specific behavioural phenotype and a high predisposition to psychiatric comorbidity. This study examines the psychiatric care situation of people with PWS. METHOD: A structured online questionnaire was administered to carers of people with PWS living in Germany, asking about demographic, diagnostic and treatment parameters as well as personal experiences. RESULTS: Of 77 people with PWS, 44.2% had at least one psychiatric comorbid diagnosis. The main reasons for seeking psychiatric care were emotional outbursts and aggressive behaviour. 34.9% reported that they were currently seeking psychiatric care without success. However, 32.5% of PWS had been treated with psychotropic medication, mainly antipsychotics. CONCLUSIONS: Psychiatric comorbidity appears to be undertreated in PWS, especially in the ambulatory setting. Uncertainty among mental health care providers may also lead to frequent off-label use of psychotropic medications.
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Comorbidade , Transtornos Mentais , Síndrome de Prader-Willi , Humanos , Síndrome de Prader-Willi/tratamento farmacológico , Masculino , Feminino , Adulto , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem , Alemanha/epidemiologia , Adolescente , Psicotrópicos/uso terapêutico , Serviços de Saúde Mental/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de SaúdeRESUMO
The significance of neurological soft signs (NSS) in major depressive disorder (MDD) remains unclear and the stability of NSS in relation to antidepressant treatment has never been investigated. We hypothesized that NSS are relatively stable trait markers of MDD. We thus predicted that patients show more NSS than healthy controls, irrespective of illness duration and antidepressant treatment. To test this hypothesis, NSS were assessed in chronically depressed, medicated MDD patients before (n = 23) and after (n = 18) a series of electroconvulsive therapy (ECT). In addition, NSS were assessed once in acutely depressed, unmedicated MDD patients (n = 16) and healthy controls (n = 20). We found that both chronically depressed, medicated MDD patients and acutely depressed, unmedicated MDD patients showed more NSS than healthy controls. The degree of NSS in both patient groups did not differ. Importantly, we found no change in NSS after on average eleven sessions of ECT. Thus, the manifestation of NSS in MDD seems to be independent of illness duration and pharmacological and electroconvulsive antidepressant treatment. From a clinical perspective, our findings corroborate the neurological safety of ECT.
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Transtorno Depressivo Maior , Eletroconvulsoterapia , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Resultado do Tratamento , Antidepressivos/uso terapêutico , FenótipoRESUMO
OBJECTIVE: Geriatric patients account for a significant proportion of the collective treated by psychiatric consultation service in hospitals. In the Emergency Department (ED), psychotropic drugs are frequently recommended, notwithstanding their extensive side-effect profiles. This study sought to investigate medication safety of geriatric patients referred to psychiatric consultation service in the ED. METHODS: Medication lists of 60 patients from the general internal medicine and trauma surgery EDs referred to psychiatric consultation service were analyzed. Utilizing PRISCUS list and Fit fOR The Aged (FORTA) classification, prescriptions of potentially inappropriate medications (PIMs) were assessed. RESULTS: 84 drugs were newly prescribed following psychiatric consultations. The total number of drugs per patient was 5.4 ± 4.2 before psychiatric consultation and 6.5 ± 4.2 thereafter (p < .001). 22.6 % of the newly recommended drugs were PIMs according to the PRISCUS list, while 54.8 % were designated as therapeutic alternatives to PIMs. 54.8 % and 20.2 % of the newly recommended drugs were FORTA category C and D drugs, respectively. An average of 1.2 ± 1.7 drug-drug interactions (DDIs) existed before psychiatric consultation and 1.3 ± 1.9 DDIs thereafter (p = .08). CONCLUSION: The majority of newly recommended drugs by psychiatric consultation service in the ED were designated as suitable therapeutic alternatives to PIMs according to the PRISCUS list, but had comparatively unfavorable ratings according to the FORTA classification, demonstrating discrepancies between these two PIM classification systems. Physicians delivering psychiatric consultation services in the ED should not solely rely on one PIM classification system.
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Prescrição Inadequada , Psiquiatria , Humanos , Idoso , Estudos Retrospectivos , Lista de Medicamentos Potencialmente Inapropriados , Serviço Hospitalar de EmergênciaRESUMO
Dear Doctor Letters (DDLs, Direct Healthcare Professional Communications) from 2011 provided guidance regarding QTc-prolonging effects with risk of torsade de pointes during treatment with citalopram and escitalopram. This study examines the DDLs' effects on prescription behavior. Data from 8842 inpatients treated with citalopram or escitalopram with a primary diagnosis of major depressive disorder (MDD) were derived from a European pharmacovigilance study (Arzneimittelsicherheit in der Psychiatrie, AMSP) from 2001 to 2017. It was examined to what extent new maximum doses were adhered to and newly contraindicated combinations with QTc-prolonging drugs were avoided. In addition, the prescriptions of psychotropic drugs before and after DDLs were compared in all 43,480 inpatients with MDD in the data set. The proportion of patients dosed above the new limit decreased from 8 to 1% in patients ≤ 65 years and from 46 to 23% in patients > 65 years old for citalopram versus 14-5% and 47-31% for escitalopram. Combinations of es-/citalopram with other QTc-prolonging psychotropic drugs reduced only insignificantly (from 35.9 to 30.9%). However, the proportion of patients with doses of quetiapine > 150 mg/day substantially decreased within the combinations of quetiapine and es-/citalopram (from 53 to 35%). After the DDLs, prescription of citalopram decreased and of sertraline increased. The DDLs' recommendations were not entirely adhered to, particularly in the elderly and concerning combination treatments. This might partly be due to therapeutic requirements of the included population. Official warnings should consider clinical needs.
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Transtorno Depressivo Maior , Síndrome do QT Longo , Humanos , Idoso , Citalopram/efeitos adversos , Escitalopram , Fumarato de Quetiapina , Transtorno Depressivo Maior/induzido quimicamente , Síndrome do QT Longo/induzido quimicamente , PsicotrópicosRESUMO
BACKGROUND: Differentiating depression and dementia in elderly patients represents a major clinical challenge for psychiatrists. Pharmacological and non-pharmacological treatment options for both conditions are often used cautiously due to fear of adverse effects. If a clinically indicated therapy is not initiated due to fear of adverse effects, the quality of life of affected patients may significantly be reduced. CASE PRESENTATION: Here, we describe the case of a 65-year-old woman who presented to the department of psychiatry of a university hospital with depressed mood, pronounced anxiety, and nihilistic thoughts. While several pharmacological treatments remained without clinical response, further behavioral observation in conjunction with 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed the diagnosis of frontotemporal dementia (FTD). To counter the pharmacological treatment resistance of psychotic depression, we decided to perform electroconvulsive therapy (ECT). Remarkably, ten sessions of ECT yielded an almost complete remission of depressive symptoms. In addition, the patient's delusional ideas disappeared. A follow-up 18F-FDG PET/CT after the ECT series still showed a frontally and parieto-temporally accentuated hypometabolism, albeit with a clear regression compared to the previous image. The follow-up 18F-FDG PET/CT thus corroborated the diagnosis of FTD, while on the other hand it demonstrated the success of ECT. CONCLUSIONS: In this case, ECT was a beneficial treatment option for depressive symptoms in FTD. Also, 18F-FDG PET/CT should be discussed as a valuable tool in differentiating depression and dementia and as an indicator of treatment response.
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Eletroconvulsoterapia , Demência Frontotemporal , Feminino , Humanos , Idoso , Demência Frontotemporal/complicações , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/terapia , Glucose , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Depressão/complicações , Depressão/terapia , Qualidade de Vida , Compostos Radiofarmacêuticos , Tomografia por Emissão de Pósitrons/métodosRESUMO
INTRODUCTION: Precision medicine in psychiatry is still in its infancy. To establish patient-tailored treatment, adequate indicators predicting treatment response are required. Electroconvulsive therapy (ECT) is considered one of the most effective options for pharmacoresistant major depressive disorder (MDD), yet remission rates were reported to be below 50%. METHODS: Since epigenetics of the stress response system seem to play a role in MDD, we analyzed the DNA methylation (DNAm) of genes encoding the glucocorticoid receptor (NR3C1) and proopiomelanocortin (POMC) through Sanger Sequencing. For analysis, blood was taken before and after the first and last ECT from MDD patients (n=31), unmedicated depressed controls (UDC; n=19, baseline), and healthy controls (HC; n=20, baseline). RESULTS: Baseline DNAm in NR3C1 was significantly lower in UDCs compared to both other groups (UDC: 0.014(±0.002), ECT: 0.031(±0.001), HC: 0.024(±0.002); p<0.001), whereas regarding POMC, ECT patients had the highest DNAm levels (ECT: 0.252(±0.013), UDC: 0.156(±0.015), HC: 0.162(±0.014); p<0.001). NR3C1m and POMCm decreased after the first ECT (NR3C1: p<0.001; POMC: p=0.001), and responders were less methylated compared to non-responders in NR3C1(p<0.001). DISCUSSION: Our findings indicate that both genes might play a role in the chronification of depression and NR3C1 may be relevant for ECT response prediction.
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Transtorno Depressivo Maior , Eletroconvulsoterapia , Humanos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/terapia , Pró-Opiomelanocortina/genética , Metilação de DNA/genética , Epigênese Genética , Resultado do Tratamento , Receptores de Glucocorticoides/genéticaRESUMO
Craving for alcohol is an important diagnostic criterion in alcohol use disorder (AUD) and an established predictor of future relapse. The 5-item Penn Alcohol Craving Scale (PACS) is one of the most widely used questionnaires to quantify craving and has been translated into different languages. It is assumed that the PACS constitutes one factor, although theoretical considerations suggest an additional second factor. We conducted stability and factor analyses (principal component and confirmatory factor analyses) of the German PACS (PACS-G) in samples of patients with AUD from the following three German study sites: Erlangen, N = 188 (mean age: 47.1 years, 43.5% female); Mannheim, N = 440 (45.5 years, 28.6% female); Hannover, N = 107 (48.1 years, 48.6% female). In our samples, the 2-factor solution of the PACS-G version is more stable than the internationally assumed 1-factor solution. The resulting two PACS-G subscores 'difficulty to resist' (items 4 and 5) and 'thoughts about alcohol' (items 1, 2, and 3) have an internal consistency (Cronbach's alpha) of 0.80 ≤ α ≤ 0.90, m = 0.86 and 0.86 ≤ α ≤ 0.91, m = 0.89 with an overlap of R2 = 62%. We found good convergent validity assessed via the Craving Automatized Scale-Alcohol and the Obsessive-Compulsive Drinking Scale, but also correlations with depression and anxiety assessed via the Beck's Depression and Anxiety Inventories. This study is the first to provide evidence for a 2-factor solution ('difficulty to resist' and 'thoughts about alcohol') underlying the PACS-G version.
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Alcoolismo , Fissura , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Psicometria , Alcoolismo/diagnóstico , Consumo de Bebidas Alcoólicas , Inquéritos e Questionários , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: Psychiatric patients in general, and elderly psychiatric patients in particular, are at risk of adverse drug reactions due to comorbidities and inappropriate polypharmacy. Interdisciplinary and clinical-pharmacologist-led medication reviews may contribute to medication safety in the field of psychiatry. In this study, we reported the frequency and characteristics of clinical-pharmacological recommendations in psychiatry, with a particular focus on geriatric psychiatry. METHOD: A clinical pharmacologist, in collaboration with the attending psychiatrists and a consulting neurologist, conducted interdisciplinary medication reviews in a general psychiatric ward with a geropsychiatric focus at a university hospital over a 25-week period. All clinical and pharmacological recommendations were recorded and evaluated. RESULTS: A total of 316 recommendations were made during 374 medication reviews. Indications/contraindications of drugs were the most frequently discussed topics (59/316; 18.7 %), followed by dose reductions (37/316; 11.7 %), and temporary or permanent discontinuation of medications (36/316; 11.4 %). The most frequent recommendations for dose reduction involvedbenzodiazepines (9/37; 24.3 %). An unclear or absent indication was the most common reason for recommending temporary or permanent discontinuation of the medication (6/36; 16.7 %). CONCLUSION: Interdisciplinary clinical pharmacologist-led medication reviews represented a valuable contribution to medication management in psychiatric patients, particularly the elderly ones.
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OBJECTIVE: In addition to teaching theoretical and clinical-practical skills, the development of individual moral competence should be another core concern in medical school. However, research suggests that moral competence in students of human medicine stagnates or even declines during the course of medical school. Therefore, the present cross-sectional study investigated the moral competence of medical students at the beginning of their studies and during their practical year, as well as the effects of testosterone as a neurohormone on moral judgment. METHODS: By means of a cross-sectional study, the moral judgment ability of 24 first-year and 16 practical year students of Hannover Medical School was recorded and evaluated with the Moral Competence Test (MCT) according to Lind. The testosterone serum level of the study participants was statistically related to the MCT results. RESULTS: No significant differences between first-year (mean±standard deviation (SD): 13.16±8.21) and practical year students (mean±SD: 11.24±8.07) with regard to moral competence as per the MCT were identified (p=0.36). Higher serum testosterone levels did not show a statistically significant correlation with moral competence (r=-0.09, p=0.58). CONCLUSION: Our results do not show a clear trend whether moral competence is lower in medical students in advanced semesters compared to the beginning of medical school and whether moral competence is influenced by the neurohormone testosterone. Nevertheless, it seems reasonable to implement moral competence training for medical students early, continuously, and as individually designed as possible during medical school (and to evaluate it in further studies) in order to preventively counteract stagnation or regression of moral judgment.
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Estudantes de Medicina , Humanos , Estudos Transversais , Princípios Morais , Julgamento , Avaliação EducacionalRESUMO
Antidepressants, in particular selective serotonin reuptake inhibitors (SSRIs), are the most commonly prescribed psychopharmacological drug group. Thus, a precise knowledge of the expected adverse drug reactions is indispensable. The increased risk of bleeding events is well documented, especially in patients treated with SSRIs. However, many other antidepressant drug groups have also been implicated in increasing the risk of bleeding. In the following review, the thrombocytic serotonin system and the respective targets of the different antidepressants are explained. Subsequently, the available literature on bleeding under the respective antidepressant classes or individual substances is presented, using data from meta-analyses whenever possible. In addition to the risk of bleeding in general, individual bleeding entities are also considered, such as gastrointestinal and cerebral hemorrhages. Finally, the effects of other drugs that increase the risk of bleeding (i. e., nonsteroidal anti-inflammatory drugs, platelet aggregation inhibitors and anticoagulants) in combination with antidepressant drugs are discussed. The information presented here is meant to guide practitioner's decision making regarding an appropriate antidepressant pharmacotherapy based on the patient's individual risk constellation.
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BACKGROUND: This study sought to investigate the frequency and characteristics of duplicate prescriptions (DPs) in elderly psychiatric inpatients using a novel categorisation of DPs that differentiates between appropriate duplicate prescriptions (ADPs) and potentially inappropriate duplicate prescriptions (PIDPs). METHODS: The study was conducted as a monocentric retrospective cross-sectional pilot study on the gerontopsychiatric ward of the Department of Psychiatry, Social Psychiatry and Psychotherapy of Hannover Medical School, a large university hospital in northern Germany. The outcome measures were the nature and frequency of PIDPs compared with the frequency of ADPs. RESULTS: For 92 individual patients a total of 339 medication chart reviews were conducted between April 2021 and February 2022. The median age of the study population was 73 years (interquartile range (IQR) 68-82 years); 64.6% were female. Patients' medications comprised a median of eight drugs (IQR 6-11 drugs) and 43.1% of the study population were exposed to at least one PIDP (at least one grade-1 PIDP: 39.5%; at least one grade-2 PIDP: 5.0%; at least one grade-3 PIDP: 1.5%). Sedatives were most frequently responsible for grade-1 and grade-2 PIDPs, while grade-3 PIDPs were elicited exclusively by analgesics. Nearly half of the study population (49.0%) displayed at least one ADP. CONCLUSION: Even though the clinical implications of PIDPs are not fully established to date, we recommend that physicians who treat elderly psychiatric patients pay special attention to PIDPs, especially PIDPs elicited by sedatives. Termination of PIDPs may prevent adverse drug reactions and save healthcare expenditures.
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Psiquiatria Geriátrica , Hipnóticos e Sedativos , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Transversais , Estudos Retrospectivos , Projetos Piloto , Prescrições , Analgésicos , Prescrições de MedicamentosRESUMO
Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and Dlgap2-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that DLGAP2 may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.
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Consumo de Bebidas Alcoólicas , Alcoolismo/genética , Metilação de DNA , Epigênese Genética , Proteínas do Tecido Nervoso/genética , Consumo de Bebidas Alcoólicas/genética , Animais , Epigenoma , Genótipo , CamundongosRESUMO
Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder based on a loss of paternally expressed genes in chromosome region 15q11-13. In addition to typical characteristics such as hyperphagia, PWS is evidenced by a certain behavioral phenotype. Common indicators are repetitive behaviors, temper tantrums, and self-injurious behaviors such as skin- and/or rectal picking. N-Acetylcysteine (NAC) was previously described as a promising therapeutic option for skin picking in PWS. In this case series, we retrospectively investigated the effect of pharmacotherapy with NAC in 14 individuals with PWS suffering from skin- and/or rectal picking. Treatment success was determined using the Clinical Global Impression-Improvement scale (CGI-I). The Clinical Global Impression-Efficacy index (CGI-EI) was used to put treatment success and side effects into perspective. Six of fourteen patients, all of which were female, showed improvement in symptoms (dosage 1800-2400 mg/day), whereas six patients did not show any change during treatment. Moreover, two male patients treated for solitary rectal picking showed new onset of skin picking. Across all cases, a CGI-I of 3 (corresponding to minimal improvement) was seen after 3 months of treatment, with a CGI-EI of 1.6 (corresponding to moderate efficacy). NAC remains a reasonable therapeutic option in certain cases of skin picking in PWS but provides only limited efficacy compared to previous studies on the topic. There was a higher rate of adverse drug reactions than previously reported. The results particularly suggest caution in future treatment in individuals with solitary rectal picking and reduced efficacy when coadministered with neuroleptics.
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Transtornos Mentais , Síndrome de Prader-Willi , Comportamento Autodestrutivo , Acetilcisteína/uso terapêutico , Feminino , Humanos , Masculino , Síndrome de Prader-Willi/complicações , Síndrome de Prader-Willi/tratamento farmacológico , Síndrome de Prader-Willi/genética , Estudos Retrospectivos , Comportamento Autodestrutivo/tratamento farmacológico , Comportamento Autodestrutivo/genéticaRESUMO
Adverse drug reactions (ADRs) constitute a frequent cause of hospitalization in older people. The risk of ADRs is increased by the prescription of potentially inappropriate medications for older people (PIMs). The PRISCUS list and the FORTA classification represent established tools to detect PIMs. The aim of the present study was to examine the prevalence and characteristics of PIM prescriptions on the gerontopsychiatric ward of a university hospital in Germany. To this aim, medication charts of 92 patients (mean age 75.9 ± 7.7 years; 66.3% female) were analyzed on a weekly basis until patient discharge by utilization of the PRISCUS list and the FORTA classification. Overall, 335 medication reviews comprising 2363 drug prescriptions were analyzed. 3.0% of the prescribed drugs were PIMs according to the PRISCUS list, with benzodiazepines and Z-drugs accounting for nearly half (49.3%) of all PIM prescriptions. 30.4% of the patients were prescribed at least one PRISCUS-PIM, while 43.5% of the study population took at least one FORTA class D drug. A considerable proportion of gerontopsychiatric patients were affected by PIMs; however, the overall number of PIM prescriptions in the study population was low. Further improvements in the quality of prescribing should target the use of sedating agents such as benzodiazepines and Z-drugs. Physicians should be aware of discrepancies between the PRISCUS list and the FORTA classification.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Lista de Medicamentos Potencialmente Inapropriados , Idoso , Idoso de 80 Anos ou mais , Benzodiazepinas , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Psiquiatria Geriátrica , Humanos , Prescrição Inadequada , MasculinoRESUMO
The International Classification of Diseases (10th Version) categorizes major depressive disorder (MDD) according to severity. Guidelines provide recommendations for the treatment of MDD according to severity. Aim of this study was to assess real-life utilization of psychotropic drugs based on severity of MDD in psychiatric inpatients. Drug utilization data from the program "Drug Safety in Psychiatry" (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) were analyzed according to the severity of MDD. From 2001 to 2017, 43,868 psychiatric inpatients with MDD were treated in participating hospitals. Most patients were treated with ≥ 1 antidepressant drug (ADD; 85.8% of patients with moderate MDD, 89.8% of patients with severe MDD, and 87.9% of patients with psychotic MDD). More severely depressed patients were more often treated with selective serotonin-norepinephrine reuptake inhibitors and mirtazapine and less often with selective serotonin reuptake inhibitors (p < 0.001 each). Use of antipsychotic drugs (APDs), especially second-generation APDs, increased significantly with severity (37.0%, 47.9%, 84.1%; p < 0.001 each). APD + ADD was the most used combination (32.8%, 43.6%, 74.4%), followed by two ADDs (26.3%, 29.3%, 24.9%). Use of lithium was minimal (3.3%, 6.1% ,7.1%). The number of psychotropic drugs increased with severity of MDD-patients with psychotic MDD had the highest utilization of psychotropic drugs (93.4%, 96.5%, 98.7%; p < 0.001). ADD monotherapy was observed to a lesser extent, even in patients with non-severe MDD (23.2%, 17.1%, 4.4%). Findings reveal substantial discrepancies between guideline recommendations and real-life drug utilization, indicating that guidelines may insufficiently consider clinical needs within the psychiatric inpatient setting.
Assuntos
Antipsicóticos , Transtorno Depressivo Maior , Antidepressivos/efeitos adversos , Antipsicóticos/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Pacientes Internados , Farmacovigilância , Psicotrópicos/efeitos adversosRESUMO
Obesity is often accompanied by major depressive disorder (MDD), and vice versa. Latest research findings suggest the body mass index (BMI) to play a role in antidepressant treatment response in general. Our study aims to examine whether adiposity-related parameters such as BMI, glucose homeostasis, or serum lipids are associated with remission to electroconvulsive therapy (ECT). A pilot study (PS, n = 9) and a glucose study (GS, n = 29) were conducted. Blood was withdrawn directly before and 15 min (GS) as well as 1 h (PS) after the first ECT and directly before the last one (usually an ECT series comprised up to twelve sessions). BMI was associated with remission in the PS (remitters: M = 28, SD = 2.5; non-remitters: M = 22, SD = 2.08; t(7) = 3.325, p < 0.001, d = 0.24) but not in the GS or when pooled together. Glucose and insulin levels increased significantly after a single ECT session (GS: glucose: F (2,25.66) = 39.04, p < 0.001; insulin: PS: F (2,83) = 25.8, p < 0.001; GS: F (2,25.87) = 3.97, p < 0.05) but no chronic effect was detectable. Serum lipids were neither significantly altered after a single ECT session nor during a whole course of ECT. There was no difference between remitters and non-remitters in insulin, glucose, or serum lipid levels. Our study is lacking the differentiation between abdominal and peripheral fat distribution, and the sample size is small. Unexpectedly, BMI, glucose homeostasis, and lipid serum levels did not differ in patients remitting during ECT. In contrast to recently published studies, we cannot confirm the hypothesis that BMI may have an impact on ECT response.