Annals of General Psychiatry最新文献

Background: Clinical practice suggests that older adults (i.e., ≥ 65 years of age) experience adverse drug reactions (ADRs) more often than younger patients (i.e., < 65 years of age). ADRs such as falls, extrapyramidal symptoms (EPS), metabolic disorders, sedation, and delirium are particularly worrisome and often associated with psychotropic drugs.

Methods: This observational study investigated the risk for psychotropic drug-related ADRs in older (n = 99,099) and younger adults (n = 363,562) in psychiatric inpatients using data from the German pharmacovigilance program "Arzneimittelsicherheit in der Psychiatrie" (AMSP) from 1993-2016. The aim was to assess whether age influenced the risk of specific ADR types and if certain psychotropic drugs posed particular concerns.

Results: The risk for ADRs did not differ between older and younger patients (relative risk 0.98, 95% confidence interval 0.92-1.05). However, older patients had a higher risk for delirium (2.35, 1.85-2.99), hyponatremia (3.74, 2.85-4.90), and orthostatic syncope (2.37, 1.72-3.26), as well as certain types of EPS, e.g., parkinsonism (1.89, 1.45-2.48) and Pisa-/metronome syndrome (3.61, 2.51-5.18). The risk for other ADRs, such as acute dystonia (0.20, 0.10-0.37), akathisia (0.47, 0.29-0.76), liver dysfunction (0.63, 0.48-0.82), weight gain (0.07, 0.04-0.14), sexual dysfunction (0.03, CI 0.00-0.25), and hyperprolactinemia/galactorrhea (0.05, 0.02-0.17) was significantly lower for older patients. Older patients treated with any type of antidepressant drug (1.33, 1.26-1.40)-especially selective serotonin reuptake inhibitors (1.57, 1.26-1.40) and selective serotonin-norepinephrine reuptake inhibitors (2.03, 1.80-2.29)-and lithium (1.74, 1.52-2.00) had a higher ADR risk than younger patients. Second-generation antipsychotic drugs had a lower (0.74, 0.71-0.77) and low-potency first-generation antipsychotic drugs a higher (1.19, 1.07-1.33) ADR risk in older patients. The risk for ADRs involving multiple drugs was higher in older patients (1.28, 1.22-1.34). ADRs in older patients were 6.4 times more likely to result in death.

Conclusions: Clinicians and pharmacists should be aware of the types of ADRs and high-risk drugs across age groups and provide appropriate monitoring. Pharmacovigilance is crucial in psychiatric patients of all ages and should not be neglected, even for drugs generally considered "safe".

Background: Schizophrenia (SCZ) is a chronic, disabling mental illness with a high disease burden and is often comorbid with metabolic syndrome (MetS). The aim of this study was to determine the prevalence of MetS in young, clinically stable, olanzapine-exposed patients with SCZ and to explore predictive factors affecting the development and severity of MetS.

Methods: A total of 274 patients with SCZ who met the inclusion criteria were enrolled in this study, and their demographic data and general clinical information were collected. Concurrently, patients were assessed for psychopathology, illness severity, and antipsychotic drug-related adverse effects.

Results: The prevalence of MetS in the target population was 35.77%, and the MetS subtype of abdominal obesity + high triglycerides + low level of high-density lipoprotein cholesterol accounted for the majority of patients in the MetS subgroup. Binary logistic regression showed that body mass index (BMI), uric acid (UA), thyroid-stimulating hormone, and QT-c interval could significantly and positively predict the development of MetS. Multiple linear regression showed that olanzapine concentration, BMI, and UA could significantly and positively predict higher MetS scores.

Conclusion: This study reports the clinical patterns of MetS in young, clinically stable, olanzapine-exposed patients with SCZ and identifies the correlations influencing the development and severity of MetS. These findings could potentially be applied toward the prevention of and intervention in MetS.

Background: Nicotine use and nicotine use disorder (NUD) are the leading causes of preventable death in the United States. Persons with mental disorders  (e.g., bipolar disorder) are differentially susceptible to nicotine use. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity and show preliminary evidence of efficacy in addiction-related behaviours. Herein, we synthesize extant preclinical and clinical evidence evaluating the effect of GLP-1RAs on neurobiological systems and behaviours salient to nicotine consumption and cessation.

Methods: Online databases (MedLine, Embase, AMED, PsychINFO, JBI EBP Database, PubMed, Web of Science, Google Scholar) were searched from inception to May 21, 2024. Relevant studies were also extracted from the reference lists of the obtained articles. All articles were screened against inclusion and exclusion criteria.

Results: Administration of GLP-1RAs reduced nicotine self-administration and nicotine-seeking behaviour in animal models that, in some cases, is sustained beyond exposure to the agent. GLP-1RAs also mitigated post-nicotine cessation weight gain, craving, withdrawal, and hyperphagia. The preceding effects are attributable to modulation of reward-related brain regions (e.g., mesolimbic dopamine system), resulting in nicotine aversion. GLP-1RAs were also efficacious as adjunctive therapies [e.g., in combination with nicotine replacement therapies (NRTs)].

Conclusion: The multi-effect characteristics in NUD paradigms provide a compelling rationale for large, adequately powered, long-term, randomized controlled trials of GLP-1RAs in the treatment and prevention of NUD. The replicated effect on mitigating post-nicotine cessation weight gain is a differentiating feature of GLP-1RAs from extant proven therapies for NUD.

Introduction: Gender- and age-specific research on medications is essential for personalizing treatment plans, optimizing dosing, minimizing adverse effects and improving outcomes. Women are twice as likely to be diagnosed with major depressive disorder (MDD), and it is commonly reported during their reproductive years. This post-hoc pooled analysis evaluated the efficacy of sertraline (one of the most studied medications in women) in women of reproductive age (18-44 years).

Methods: Data was pooled from nine clinical trials of sertraline that included 1832 subjects with MDD. The analysis set included 1097 women, 651 of those were of reproductive age. Sertraline was compared with placebo for changes in total HAM-D17 and CGI scores measured over time through MMRM analysis. The change from baseline to the end of study (-week 8) was assessed using ANCOVA.

Results: The changes from baseline in total HAM-D17 and CGI scores were significantly higher for sertraline than for placebo at the end of 8 weeks for all women (LS Mean difference, 95% CI: -1.81(-3.01,-0.62), P = 0.0029; -0.38(-0.55,-0.20), P < 0.0001, respectively). For women of reproductive age these changes (LS Mean difference, 95% CI: -2.08(-3.52,-0.64), P = 0.0047; -0.44(-0.66,-0.22), P < 0.0001, respectively), were significant from week 2 (HAM-D17) and week 1 (CGI) till the end of study.

Limitations: Only sertraline and placebo arms were included in the analysis. The dosing varied between studies, and the effect of dose was not addressed.

Conclusions: Sertraline is an effective option for treatment of MDD in women, including those in the childbearing age.

Background: Although second-generation antipsychotics (SGAs) have proven to be effective therapeutic options for patients with schizophrenia, there is a notable lack of evidence on patients' subjective perspectives regarding their well-being, quality of life, and satisfaction with these medications. This study aimed to evaluate the treatment satisfaction and effectiveness of lurasidone on quality of life and functioning in adult patients with schizophrenia in real-world Italian clinical practice.

Methods: This was a multicentre, national, non-interventional, single-arm, 3-month prospective study. Patients who were naive to lurasidone treatment and whose treating physician had decided to start them on this medication were enrolled and evaluated over a 3-month period. Eligible patients were adults (≥ 18 years of age) with a primary diagnosis of schizophrenia who were being treated with lurasidone (for the first time [i.e., they were lurasidone naive]) as part of routine clinical practice. Efficacy endpoints were changes in patient/caregiver treatment satisfaction (seven-point Likert scale from the Treatment Satisfaction Questionnaire for Medication), patient quality of life and functioning (QLS), investigator-rated global assessment of functioning (CGI-S, IAQ) after 6 weeks and 3 months of lurasidone, and number of relapses and hospitalizations.

Results: Sixty-one patients were enrolled and 59 completed the study. The median dosage of lurasidone at baseline was 37.00 mg/day. The median duration of titration was 86.0 days (Min 28; Max 115 days); the median number of dosage changes was 1.0. At the end of 3-month observation period, the median dose of lurasidone was 74.00 mg/day. QoL and Functioning Score showed a trend of improvement over time, reaching a mean change from baseline of 9.8 at the end of the study. According to the CGI-S, the percentage of patients who were "markedly or severely ill" showed a continuous decrease from baseline to 3 months, from 62.29% to 8.20%. Patient satisfaction increased over time, with 80.32% of patients reporting that they were somewhat, fairly, or very satisfied (including 63.93% who were completely or very satisfied) at the end of the study. No relapses/hospitalizations for psychiatric reasons were reported. Lurasidone was well tolerated with no safety concerns or discontinuations due to AEs.

Conclusions: Lurasidone represents a valid option for the treatment of schizophrenia and positively affects subjective well-being, quality of life and satisfaction.

Trial registration: NCT06527885 retrospectively registered (01/08/2024).

Background: The association between Attention-deficit hyperactivity disorder (ADHD) and suicidality has been subject of growing interest for research in the latest years. Suicidality was generally assessed categorically and without the use of validated instruments, leading to heterogeneous or even conflicting evidence. The prevalence of both suicidal ideation and attempts varies considerably, and the associated risk factors remain unclear. Our study investigated suicidality in ADHD using a dimensional approach and a validated and internationally recognized instrument. Our primary aim was to evaluate the prevalence of suicidal ideation (SI), severe suicidal ideation (SSI), suicidal behavior (SB) and non suicidal self-injury behavior (NSSIB) in a sample of adult patients with ADHD. The second objective was to identify sociodemographic and clinical features associated with increased risk of suicidality in these patients.

Methods: The sample included 74 adult patients with clinical diagnosis of ADHD. Suicidality was assessed by administering the Columbia-Suicide Severity Rating Scale. Logistic regressions were used to examine predictors of SI, SSI, SB and NSSIB.

Results: The lifetime prevalence of SI and SSI were 59.5% and 16.2%, respectively. The 9.5% of patients showed lifetime SB, while NSSIB was found in 10.8% of the subjects. Lifetime SI was associated with severity of inattentive symptoms during adulthood, low self-esteem and impairment in social functioning. Lifetime SSI appeared related to severity of inattentive symptoms during childhood, attentional impulsiveness and number of hospitalizations, while physical activity appeared to be protective. The prevalence of lifetime SB and NSSIB did not appear significantly related to any socio-demographic or clinical feature.

Conclusions: Adults with ADHD should be considered at risk of suicide and it is important to determine which patients are at higher risk, in order to guide preventive interventions. The association between ADHD and suicidal ideation did not appear to be influenced by psychiatric comorbidities, but rather by inattention itself, which represents the core symptom of ADHD.

Background: Major Depressive Disorder (MDD) is a leading cause of disability and results in excessive utilization of healthcare resources worldwide. The Middle East and North Africa (MENA) region shows a high prevalence of depressive disorders. Generalized Anxiety Disorder (GAD) and MDD have the highest rate of comorbidity of all mood and anxiety disorders, ranging from 40 to 98% in drug studies. Comorbid GAD results in more significant impairment in MDD and increases the severity of symptoms. Although several clinical trials supported the safety and effectiveness of vortioxetine, no data regarding these aspects has been revealed in the MENA region. This study aimed to assess the safety and efficacy of vortioxetine in patients with comorbid GAD in the United Arab Emirates (UAE).

Method: In a multicenter observational study, 118 patients with confirmed anxiety and depressive disorders were evaluated over four visits (baseline visit, two weeks, four weeks, and eight weeks) using MADRS and HAM-A scales to assess depression and anxiety severity, respectively by calculating mean change and the percent using Kendall's W test.

Results: A significant mean difference in MADRS score was observed, with a gradual decrease of mean MADRS total scores over the assessment weeks (p < 0.001) as well as in HAM-A scores, from severe to moderate-severe anxiety through the four visits (p < 0.001). Furthermore, only one case was reported as a serious side effect. Nausea and insomnia were the most predominant side effects reported among the studied population.

Conclusion: Vortioxetine was found effective and safe among patients with MDD and comorbid GAD.

Background: Schizophrenia and substance use disorders (SUDs) are often comorbid conditions that present clinical challenges due to their heterogeneity and the difficulties associated with poor physical health, low medication adherence, high relapse and hospitalization rates, and increased risk of mortality. This is often exacerbated by a fragmented health care system that treats addiction and mental illness separately, leading to delays in proper diagnosis and treatment.

Main text: The aim of this narrative review, based on an extensive literature search and experts' clinical experience, is to synthesize evidence on the psychopathological and clinical characteristics of patients, the burden and management at the level of healthcare system, and possible gaps in the treatment of schizophrenia with comorbid SUD in order to understand and address the needs of patients. Treatment options, differences between antipsychotic medications, and the benefits of long-acting formulations and partial dopaminergic agonists are described. Partial dopamine agonists (aripiprazole, cariprazine, and brexpiprazole) have demonstrated good control of psychotic symptoms and SUDs with a favorable safety profile.

Conclusion: Pharmacological interventions should be accompanied by psychosocial support within an integrated and multidisciplinary approach that promotes shared decision-making and a good therapeutic alliance between the entire medical team and the patient.

Introduction: Bipolar disorder is a psychiatric condition commonly treated with lithium. This treatment has various biological effects on the brain; however, variability in the areas and types of changes as a result of lithium treatment has resulted in discourse over lithium's effect. As a result, a comprehensive synthesis is needed to understand lithium's true neurological effect. This review aims to identify a common result of lithium use in the neurobiology of bipolar patients, specifically in the amygdala, to determine whether volumetric changes in the amygdala are a common effect.

Methods: We conducted a preliminary search to identify key search terms across electronic databases, including Google Scholar and PubMed. After screening and application of inclusion and exclusion criteria, 9 cross-sectional studies were identified.

Results: The evidence from these cross-sectional studies showed either an increase or no change in amygdalar volume. While this fails to identify a definite pattern in amygdalar volume changes, it highlights a need for further research to identify sources of heterogeneity and minimize them to ascertain accurate results.

Conclusions: The present review may be used to influence future work concerning neurobiological changes in the amygdala as a result of lithium treatment for bipolar patients by summarizing patterns in the current literature.

Objectives: This study aims to reveal the current knowledge map, research hotspots of functional magnetic resonance imaging (fMRI) studies on depression, as well as identify the brain regions associated with depression.

Methods: CiteSpace was conducted to analyze the publication outputs, country, institution, cited journals, author and cited author, references, keyword cocurrence and burst keywords of fMRI studies in depression from 2010 to 2024. And a meta-analysis of fMRI was used to identify brain regions associated with depression using Neurosynth.

Results: A total of 4,049 publications were included, and Gong Qiyong was the most prolific authors. Neuroimage, Biological Psychiatry, and Human Brain Mapping were prominent journals. Default mode network (DMN), prefrontal cortex, amygdala, and anterior cingulate cortex were the popular keywords. The fMRI studies on depression have mainly focused on major depression, especially the DMN. Functional connectivity and regional homogeneity of brain regions were research hotspots. The meta-analysis revealed significant differences in brain regions between patients with depression and healthy controls, including the Amygdala_L, Insula_R, Frontal_Inf_Oper_R, Cingulum_Post_L, Putamen_L, Thalamus_R, Angular_L, Precuneus_R, Frontal_Sup_R, Occipital_Inf_L.

Conclusions: This study sheds light on key issues and future directions in fMRI research on depression, elucidating the brain regions related to depression.