Acta Psychiatrica Scandinavica最新文献

Introduction: Cognitive side effects, such as memory loss, associated with electroconvulsive therapy (ECT) have been extensively studied. However, knowledge about (sub)acute confusional states during ECT is limited, particularly in older adults with depression. Their incidence, recurrence, and co-occurrence remain unclear. This study aimed to describe the incidence, recurrence, co-occurrence, and clinical course of various subtypes of confusional states during ECT.

Methods: Data were derived from the 'Rivastigmine for ECT-induced Cognitive Adverse effects in Late-Life depression' (RECALL) prospective cohort study, involving 145 older adults (≥ 55 years) with a major depressive episode receiving ECT. We assessed different subtypes of confusional states: postictal and interictal delirium (PID and IID), postictal agitation (PIA), prolonged time to reorientation (TRO), and subacute general cognitive decline (Mini Mental State Examination decline ≥ 4 points) throughout the ECT course.

Results: Over half of the older adults (55.9%) experienced at least one subtype of confusional state during their ECT course. The most prevalent subtypes were PIA (29.5%) and prolonged TRO (28.3%), while postictal (5.9%) and interictal delirium (4.2%) were less common. Recurrence rates varied, with interictal delirium (66.7%) and prolonged TRO (50.0%) showing the highest rates compared to postictal delirium (12.5%). Notably, 18.0% of older adults experienced more than one subtype of confusional state during their ECT course, and these states could emerge at any time during the ECT course.

Conclusion: This is the first study to comprehensively examine the clinical course of various subtypes of confusional states during ECT in older adults with depression Our findings reveal that confusional states are highly prevalent, heterogeneous, and may emerge at any time during the ECT course. Notably, since the instruments used were not designed to measure (subtypes of) confusional states during ECT, further research into the differentiation of (sub)acute confusional states is warranted.

Trial registration: EudraCT 2014-003385-24.

Objectives: Despite the high prevalence of alcohol use disorder (AUD), only a minority of patients receive recommended pharmacological treatments, possibly owing to uncertainty about the real-world effectiveness of these medications. Here, we analyzed nationwide, register-based data to investigate the association between approved AUD medications (naltrexone, acamprosate, disulfiram, and nalmefene) and the risk of alcohol-related hospitalizations among individuals with AUD.

Methods: People aged 18-64 with a registered first-time diagnosis of AUD between 2009 and 2019 (N = 93,727) were identified from the Swedish National Patient Register. Cox regression models were used to analyze the association between AUD medication exposure and the risk of alcohol-related hospitalizations.

Results: Exposure to naltrexone (hazard ratio [HR] = 0.80; 95% confidence interval [CI] = 0.73-0.87) or disulfiram (HR = 0.83, 95% CI = 0.79-0.88) as monotherapy, or a combination of naltrexone/disulfiram (HR = 0.68, 95% CI = 0.49-0.96), or disulfiram/acamprosate (HR = 0.57 95% CI = 0.44-0.74) was significantly associated with a lower risk of alcohol-related hospitalizations compared to periods without exposure to any of these medications. In contrast, no significant associations were observed for acamprosate, nalmefene, or the combination of acamprosate/naltrexone. Sensitivity analyses in individuals with severe AUD and stratified subgroup analyses by different socioeconomic groups confirmed the robustness of the results.

Conclusion: Results indicate a significant association between disulfiram and naltrexone monotherapy, as well as the combination of disulfiram with naltrexone or acamprosate, with a lower risk of alcohol-related hospitalizations among individuals with AUD. Low prescription rates suggest that AUD medications are currently underutilized. Increasing the availability of these medications for individuals with AUD could help reduce alcohol-related hospitalizations.

Aims: Both inflammation and smoking are known to affect clozapine metabolism. However, the impact of inflammation on clozapine metabolism in relation to smoking status is unclear. Therefore, we investigated correlations between C-reactive protein (CRP) and clozapine levels in smokers and non-smokers separately.

Methods: Patients were included retrospectively from a therapeutic drug monitoring (TDM) service in Oslo, Norway, during January 2005-April 2022. Inclusion criteria were known smoking status and CRP measurements no longer than 7 days before or after clozapine TDM. Exclusion criteria were confirmed blood sampling for TDM outside 10-30 h after the last clozapine intake. Information about clozapine dosing was retrieved from the requisition forms.

Results: In 126 patients fulfilling the criteria (47% smokers), dose-adjusted serum concentration (CD) of clozapine correlated significantly with CRP in non-smokers (R = 0.492; p < 001) but not in smokers (R = 0.191; p = 0.166). When subgrouping non-smoking patients into low CRP (< 5 mg/L; reference [51% of the population]), mid CRP (5-50 [37%]) and high CRP (> 50 [12%]), clozapine CD gradually increased in mid- (+48%, p = 0.004) and high-CRP groups (+204%, p < 0.001) compared with the low-CRP group. No significant differences in clozapine CD were found between CRP groups among smokers (p > 0.15).

Conclusions: We report a significant correlation between CD of clozapine and CRP levels in non-smoking patients only. In these patients, clozapine CD is more than 3-fold higher at CRP > 50 versus CRP < 5. This suggests that non-smokers are most susceptible to clozapine side effects during inflammation or infection and represent patients where TDM analyses are especially important for guiding clozapine dosing.

Background: Mental disorders are associated with excess risk of death from unnatural and natural causes, but few studies have differentiated causes of death among patients with major depression. We examined cumulative and relative risks of all-cause and cause-specific mortality in individuals with major depression up to 50 years after diagnosis according to sex, age, and time since depression diagnosis.

Methods: In this nationwide matched-cohort study, we included individuals diagnosed with major depression in Danish National Patient registries from 1970 through 2021 and a 1:5 matched sample of the general population (reference population). Individuals were followed for their underlying cause of death in the Danish Cause of Death Registry up to 2022, and we estimated cumulative risk and hazard ratios for all-cause and 10 specific causes of death.

Results: The study included 330,577 adults diagnosed with major depression in Denmark (median age at first diagnosis, 45 years; 63.4%women) and 1,652,885 members of the matched reference population (median age, 45 years; 63.4%women). During the study period, 116,628 (35.2%) individuals with depression and 389,135 (23.5%) matches from the reference population died. Individuals with depression had considerably higher mortality risk at all time periods and ages compared to the reference population, and the increased risk was most pronounced in the first year after diagnosis. The lifetime risk of suicide was 11.2% in individuals with depression compared with 1% in the reference population, and before age 65 years, suicide was the leading cause of death in patients with depression. When compared with the reference population, individuals with depression also exhibited a higher risk of various specific natural causes of death before the age of 85 years.

Conclusions: The risk of death from suicide and medical disorders is elevated in individuals with depression, especially the first year after diagnosis. Because a large number of deaths can be attributed to depression shortly after onset, clinicians should be aware of this risk.

Background: Metformin shows potential in combating clozapine-induced weight gain (CIWG). However, current evidence for its use remains limited. Through an audit we determined the prevalence of metformin use among clozapine-treated patients and its impact on weight and waist circumference (WC).

Methods: This retrospective cohort study examined electronic medical records of community-based clozapine patients under the care of metropolitan community mental health teams within the Central Adelaide Local Health Network (CALHN) from January 2014 to June 2023. We included patients treated with clozapine both with and without metformin, above 18 years of age, with complete physical monitoring data at baseline, 6, and 12 months.

Results: There were 357 patients, who met study criteria. Metformin was prescribed to 23% of patients, of whom 78% had diabetes. At baseline, WC was > 101 cm in 71% of males and > 87 cm in 86% of females, placing them at increased risk of weight-related comorbidities, including cardiovascular disease, cancer, and death. After 1 year, males and females in the highest risk group for WC-related comorbidities increased to 76.3% and 95.4%, respectively. Co-prescription of metformin with clozapine was associated with unadjusted mean weight loss (-1.67 kg) and decrease in WC (-1.00 cm). Patients not using metformin gained weight (0.68 kg) and WC (2.49 cm). Using a linear mixed-effects models adjusting for repeated measurements, age, sex, and type 2 diabetes, over 12 months, patients treated with metformin were 3.08 kg lighter than those not taking metformin (95% confidence interval [CI]: 0.54-5.62, p = 0.018). Similar models suggested patients treated with metformin showed an average 2.83 cm decrease in WC compared with those not taking metformin (CI: 0.26-5.40, p = 0.03). There was no significant interaction between difference from baseline in weight or WC and metformin dose (p > 0.05).

Discussion/conclusion: The prevalence of metformin use for CIWG appears low in this cohort, where over 84% of patients were overweight or obese. Metformin use was associated with a significantly lower incidence of weight and WC gain over 12 months. Pharmacists are crucial for educating clinicians and patients about the benefits of metformin for reducing CIWG.

Objectives: Recurrent [hypo]mania without major depressive episodes ("unipolar mania" [UPM]) is an uncommon form of major affective disorder related to bipolar disorder (BD). We characterized UPM patients and estimated the prevalence of their characteristics based on prolonged times-at-risk.

Methods: Using standard bivariate and multivariate statistics, we compared the characteristics of 63 consecutive UPM patients to 1210 other BD patients over prolonged, close, prospective follow-up at expert mood disorder centers.

Results: UPM was uncommon (4.95% of 1273 BD cases during 18.2 years at risk) with a 2.5-fold excess of men and 93.4% considered type I BD. UPM cases had earlier initial clinical interventions than other BD patients, more psychotic features with first episodes, and fewer UPM patients were married but did not have fewer children and were more unemployed. UPM cases experienced more morbidity (episodes and hospitalizations/year and %-time ill) than other BD patients and made more follow-up clinic visits/year. They were less likely to be suicidal and had less general medical comorbidity but did not differ in substance abuse. They had lower ratings of depressive symptoms, used mood stabilizers more, and as expected, received antidepressants 27 times less than other BD patients. Observed rates of UPM declined with longer observation times.

Conclusions: UPM was uncommon (4.95% of BD cases; 0.31% with hypomania only). Compared to ordinary BD, UPM had significantly greater morbidity and unemployment but a lower risk of suicidal behavior or general medical disorders associated with bipolar depression. This unusual disorder needs greater recognition, clarification of its nosological status, and efforts to optimize its treatment.

Introduction: Gestational exposure to valproate has been associated with a wide range of adverse pregnancy outcomes, including major congenital malformations in offspring. However, to date, no meta-analysis has comprehensively examined the risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in children gestationally exposed to valproate.

Methods: We searched MEDLINE, Embase, and Scopus from inception until 15 May 2024 for relevant English-language articles. Primary outcomes of interest were the risk of ASD and ADHD, two independent primary outcomes, in children exposed to valproate anytime during pregnancy relative to unexposed children. Secondary outcomes were trimester-wise analyses of risk. We used a random effects model to pool the overall and trimester-wise hazard ratios (HRs) and obtained 95% confidence intervals (CIs), separately for the risks of ASD and ADHD. Study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist.

Results: Eight cohort studies (pooled N = 6,033,300) met our search criteria. Anytime gestational exposure to valproate was associated with a large increase in the risk of ASD (adjusted HR [aHR], 3.10; 95% confidence interval [CI], 2.24-4.28; N = 1,841,198) and a modest increase in the risk of ADHD (aHR, 1.62; 95% CI, 1.30-2.01; N = 24,295). The findings in sensitivity analyses for both outcomes were generally consistent with those of the main analyses. Notably, anytime gestational exposure to high-dose valproate (> 1.0 to 1.1 g/day) was associated with a substantially elevated risk of ASD (aHR, 6.32; 95% CI, 3.12-12.80, N = 1,719,825). Likewise, in monotherapy (aHR, 4.21; 95% CI, 2.97-5.95; N = 1,745,253) and discordant sibling pair (aHR, 6.42; 95% CI, 2.02-20.42; N = 1133) analyses, the risk of ASD was substantially elevated.

Conclusion: Gestational exposure to valproate was associated with an increased risk of ASD and ADHD; the risks for ASD were greater at doses ≥ 1000 mg/day. These findings add to the literature that strongly discourages the use of valproate by women of childbearing age, especially during pregnancy.

Introduction: Childhood maltreatment (CM) and depression are serious global issues with high prevalence and lifelong impacts on physical and mental health. CM has been proposed as a modifiable risk factor for depression that, if prevented, may contribute to a reduction in the global incidence of depressive disorders. Despite this, there is a paucity of reviews examining the strength of the association between these variables. The aim of this systematic review and meta-analysis was to evaluate the empirical evidence and determine if CM is supported as a preventable risk factor for depression.

Methods: A search was performed in July 2024 for all peer-reviewed journal articles written in English examining the relationship between CM and adult depression in the electronic databases EBSCOhost, Proquest, and Embase. Studies were included in this review if they measured maltreatment before 18 years of age as the independent variable and adult depression as the dependent variable. Studies were excluded if the outcome variable was grouped with comorbidity and if they did not report primary quantitative data. A total of 77 studies with 516,302 participants met the inclusion criteria for review.

Results: A random-effects meta-analysis was used to generate a pooled odds ratio from 87 effect estimates and demonstrated that individuals with a history of any CM are 2.5 times more likely to experience adult depression (OR = 2.49 [95% CI: 2.25-2.76]). This increase in odds remained regardless of how the primary studies screened for depression.

Conclusions: These findings confirmed the strong association between the experience of CM and adult depression. High heterogeneity in the meta-analytic results also suggested that further research is required that applies consistent adjustments for comorbidities and confounding factors and examines the temporal relationship between the variables to establish causality.

Introduction: Depressive disorders are a leading cause of global disease burden, particularly with the challenge of treatment-resistant depression (TRD). Research points to a complex bidirectional relationship between cardiovascular (CV) risk factors and TRD, with CV risk negatively impacting brain structure and potentially influencing antidepressant resistance. Moreover, the association between depression and the genetic vulnerability to cardiovascular disease suggests a shared pathophysiological process between the two. This study investigates the mediating role of brain structural alterations in the relationship between CV and cerebrovascular (CeV) risk and treatment resistance in depression.

Methods: We assessed 165 inpatients with Major depressive disorder. Each patient's CV risk was assessed via the QRISK 3 calculator. For a subset of patients, CV and CeV disease polygenic risk scores (PRS) were obtained. All patients underwent a 3 T MRI scan, and white matter hyperintensities estimates and indicators of brain trophic state were obtained.

Results: Both CV risk and CV disease PRSs are associated with treatment resistance status, white matter hyperintensities, and indicators of brain atrophy. Mediation analyses suggested that CV-induced brain alterations might underlie the relation between CV genetic and phenotypic risk and antidepressant treatment resistance.

Conclusion: These results underscore the need to explore cardiovascular risk management as part of treatment strategies for depression, pointing toward a shared pathophysiological process linking heart and brain health in treatment-resistant depression.