Therapeutic Advances in Psychopharmacology最新文献

Background: Despite the therapeutic benefits, non-adherence to lithium is common. One recent study showed that most patients discontinue lithium due to adverse effects. Little is known about individuals starting and discontinuing lithium repeatedly.

Objectives: We aimed to determine reasons for discontinuing and restarting lithium multiple times in patients with bipolar or schizoaffective disorder.

Design: Retrospective cohort study based on psychiatric case records of the SLaM Biomedical Research Centre Case Register (SLaM BRC case register).

Method: Anonymised clinical data were extracted via the Clinical Record Interactive Search (CRIS) application. Patients with at least three events of lithium discontinuation between 2012 and 2022 were included.

Results: Of 2888 eligible patients, 123 patients had discontinued lithium on at least three occasions. Psychiatric reasons, such as suspected lack of insight, feeling subjectively well or disagreeing with diagnosis, were the most common reasons for lithium discontinuations. They accounted for 77.2% of cases in the first event of discontinuation, 73.2% in the second and 72.3% in the third event. Adverse physical effects accounted for 19.5% of cases in the first event of discontinuation, 25.2% in the second and 26.0% in the third event. Relapse into the underlying affective disorder accounted for 83.7% each of reinstatements in the first and second events and 82.1% in the third event.

Discussion: In our sample, lithium was discontinued due to adverse effects in only a minority of patients. In most cases, the reasons for lithium discontinuation were considered psychiatric. Lithium was mainly restarted due to relapse. This warrants a better understanding of the reasons for repeatedly discontinuing lithium and the best way to promote lithium adherence to prevent a perpetual cycle of remitting when on lithium and relapsing when off lithium.

Background: Long-acting injectable (LAI) antipsychotics have been shown to improve adherence and clinical outcomes in schizophrenia treatment. However, issues with compliance and early discontinuation of LAIs remain a significant challenge in real-world settings. Understanding the factors influencing successful initiation and maintenance is essential to maximize their clinical benefits.

Objectives: This study aimed to investigate factors associated with the maintenance of paliperidone LAI (PLAI) during the first year of treatment in a real-world clinical setting, focusing on initiation practices and baseline clinical factors.

Design: This was a non-interventional, retrospective observational study conducted at three hospitals in South Korea. Data were collected from electronic medical records from January 2010 to January 2023.

Methods: This study included 664 patients who initiated PLAI treatment. Kaplan-Meier survival analysis and multivariate Cox proportional hazards models were used to evaluate clinical and demographic factors influencing the 1-year discontinuation rate.

Results: The 1-year discontinuation rate was 51.5% (342/664), with most discontinuations occurring in the early phase of treatment. Factors significantly associated with a lower risk of discontinuation included initiating PLAI with the standard starting dose of 150 mg (hazards ratio (HR) 0.766, p = 0.021), concurrent use of antipsychotics at baseline (HR 0.630, p = 0.019), a higher dose of concurrent antipsychotics (HR 0.985, p = 0.005), and outpatient initiation (HR 0.671, p < 0.001). Baseline clozapine use was associated with a lower risk of treatment discontinuation (HR 0.755, p = 0.096). A predictive model incorporating these factors demonstrated moderate ability to predict 1-year discontinuation (area under the curve (AUC) = 0.61).

Conclusion: The findings highlight the importance of adhering to the standard dosing regimen for PLAI initiation and its potential as an augmentation agent in combination with other antipsychotics. Initiating PLAI in an outpatient setting and addressing adherence challenges early in treatment may enhance long-term treatment continuity in patients with schizophrenia.

Background: People bereaved due to COVID-19 may face mental health challenges and posttraumatic growth opportunities. Resilience, as an inherent trait or ability, may protect the bereaved from developing mental health problems and facilitate growth. The Dual Process Model (DPM) is an important framework for understanding adaptation after bereavement. However, little is known about whether resilience could help with adjusting to COVID-19 bereavement and whether dual process coping plays a part in the relationship between resilience and mental health among COVID-19 bereaved individuals.

Objective: We aim to examine the relationship between resilience and symptoms of prolonged grief, posttraumatic stress, anxiety, depression, and posttraumatic growth following COVID-19 bereavement, and to investigate the role of dual process coping, which includes loss-oriented (LO) coping, restoration-oriented (RO) coping, and oscillation between LO coping and RO coping in this relationship.

Design: This is an online cross-sectional survey.

Method: A total of 408 Chinese participants who lost a close person due to COVID-19 participated in the study from September to October 2020. Demographic and loss-related information was collected. Resilience, dual process coping, symptoms of prolonged grief, posttraumatic stress, anxiety, depression, and posttraumatic growth were measured. Correlation analyses and mediation analyses were conducted to analyze the data.

Results: Resilience was negatively correlated with anxiety and depressive symptoms and positively correlated with posttraumatic growth. In the relationship between LO coping, RO coping, oscillation, and mental health, LO coping was positively associated with prolonged grief, posttraumatic stress, anxiety, and depressive symptoms, as well as posttraumatic growth; RO coping was negatively associated with prolonged grief symptoms and posttraumatic growth, and positively associated with anxiety and depressive symptoms; oscillation was negatively associated with prolonged grief, posttraumatic stress, anxiety, and depressive symptoms. In addition, mediation analysis showed that oscillation mediated the relationship between resilience and anxiety and depressive symptoms, and RO coping mediated the relationship between resilience and depressive symptoms and posttraumatic growth.

Conclusion: Our findings indicate that among individuals who have experienced bereavement due to COVID-19, RO coping serves a protective role in the relationship between resilience and depressive symptoms and a facilitative role in the relationship between resilience and posttraumatic growth. Additionally, oscillation plays a protective role in the association between resilience and symptoms of anxiety and depression. Professionals should consider the bereaved individuals' resilience, LO coping, RO coping, and osci

Citalopram is a selective serotonin reuptake inhibitor used to treat depression and various anxiety disorders, which is mainly metabolized by the P450 (CYP) enzyme. Rifampin is a rifamycin with bactericidal activity against Mycobacterium tuberculosis. Rifampin significantly induces the P450 (CYP) enzyme system, which makes it susceptible to potential drug interactions with other medications. However, there have been few reports on the possible interaction between rifampin and citalopram. We report a 76-year-old patient who had been taking citalopram 20 mg daily for long-term treatment of depression. After 2 months of rifampin treatment for tuberculosis, the patient presented with intractable depressive symptoms, insomnia, and a profound sense of hopelessness. The trough plasma concentration of citalopram was monitored, which was 8.19 ng/mL, and failed to reach the guideline-recommended effective therapeutic range (50-110 ng/mL). Based on the therapeutic drug monitoring results of citalopram, the dosage of citalopram was adjusted to 40 mg daily, resulting in a significant improvement in depressive symptoms. This case provides further evidence of a clinically significant interaction that may occur between rifampin and citalopram.

Background: Extant research on cognitive functioning in treatment-resistant schizophrenia (TRS) is limited and of poor quality. Cognitive impairments in patients with schizophrenia spectrum disorders (SSD) significantly influence quality of life. In patients with TRS, clozapine (CLO) is not consistently associated with improved cognitive functioning. The active metabolite n-desmethylclozapine (norclozapine (NCLO)) potentially exerts procognitive effects due to cholinergic and glutamatergic activity. Unfortunately, research on CLO/NCLO ratio and cognitive functioning is even more scarce.

Objectives: To review the literature on the effect of the CLO/NCLO ratio on cognitive functioning in patients with SSD.

Design: This is a systematic review.

Data sources and methods: A search was carried out in the electronic databases Embase, PsycINFO, PubMed, Cochrane and the Cochrane Controlled Register of Trials with no restrictions in language or publication year.

Results: We identified 15 relevant studies (longitudinal, k = 4; cross-sectional, k = 11). The study population consisted of adult clozapine users (n = 953) with varying degrees of treatment resistance. Specific cognitive domains and overall cognitive functioning were assessed using various neuropsychological tests and a composite score, respectively. Eleven studies were considered of fair quality (longitudinal: k = 2, cross-sectional: k = 9). In one longitudinal study, a negative causal relationship was found between the CLO/NCLO ratio and attention/vigilance and a negative correlation between social cognition and the composite score (n = 11). No significant correlations were found between the CLO/NCLO ratio and the cognitive domains processing speed, reasoning/problem solving, or for working memory (k = 1, n = 11), verbal learning (k = 1, n = 43) or visual learning (k = 2, n = 54). Study designs and populations were heterogeneous, and the analysis of confounding factors was limited and inconsistent.

Conclusion: Clinical evidence is too scarce to support the hypothesis of a procognitive effect of NCLO. Personalised CLO treatment by modulating the CLO/NCLO ratio remains a distant prospect. Recommendations for future CLO research and anticipated limitations are discussed.

Trial registration: This systematic review was preregistered with PROSPERO (CRD42023385244).

Background: Altered cerebral cortex's structural organization has been found in individuals with betel quid dependence (BQD). However, the neurological underpinnings of the BQD-related abnormalities in cortical thickness and brain circuitry deficit are largely unknown.

Objective: This study aimed to investigate potential abnormalities of brain circuitry in the cortical thickness of BQD individuals by applying the surface-based morphometry (SBM) method.

Design: Cross-sectional study.

Methods: High spatial resolution, three-dimensional T1-weighted structural imaging data were collected from 53 individuals with BQD and 37 healthy controls (HCs) who were similar to the BQD group in terms of age, sex, and educational level. The SBM method was applied to analyze the cortical thickness alterations in BQD-related areas. Independent-samples t-test was used to assess the cortical thickness difference between the two groups. Pearson correlation analysis was used to investigate the correlation between cortical thickness changes and clinical characteristics, including BQD scale scores and duration of BQD.

Results: The BQD group had a higher cortical thickness than the HC group at the lateral orbitofrontal (t = 4.703, p = 0.0028) and pars opercularis (t = 3.602, p = 0.0403) clusters in the right cerebral hemisphere, with age, sex, and education duration as covariates (p < 0.05, Monte Carlo). There were no significant differences in age, sex, or education duration-adjusted cortical thickness of the left cerebral hemisphere between BQD chewers and HCs (p > 0.05, Monte Carlo). Correlation analysis revealed that the cortical thickness of the right pars opercularis was negatively correlated with the BQD duration (r = -0.274, p = 0.047). The cortical thickness of the right lateral orbitofrontal cluster was not significantly correlated with Betel Quid Dependence Scale (BQDS) or BQD duration (p > 0.05).

Conclusion: This study demonstrated that BQD might be associated with changes in the orbitofrontal and pars opercularis cortical thickness, which may be related to the neurobiological basis of BQD.

Background: Emotional dysregulation, particularly unconscious catastrophic cognitions, plays a pivotal role in the genesis of panic disorder (PD). However, no studies have yet applied the percentage of amplitude fluctuation (PerAF) metric in resting-state functional magnetic resonance imaging to examine spontaneous neural functioning and its relation to catastrophic cognitions in PD.

Objectives: To explore the interplay between resting-state neural activity, functional connectivity (FC), and unconscious emotion regulation in individuals with PD.

Design: Cross-sectional study.

Methods: The study encompassed 51 participants, including 26 PD patients and 25 healthy individuals. The PerAF algorithm was employed to explore the local spontaneous neural activity in PD. Regions exhibiting aberrant spontaneous neural activity were used as seed points for whole-brain FC analysis. Correlations were utilized to examine associations between local neural activity patterns and neurocognitive assessments in PD.

Results: The study revealed that compared to healthy individuals, PD patients exhibited elevated PerAF values in key emotion-regulation-related brain regions, including the ventromedial prefrontal cortex (vmPFC), striatum, amygdala, dorsomedial prefrontal cortex (dmPFC), and cerebellum. In addition, the resting-state FC between vmPFC and precuneus, as well as between the cerebellum and precuneus, was weakened in PD patients. Furthermore, positive associations were noted between PerAF measurements of vmPFC and amygdala and catastrophizing scores.

Conclusion: PD involves regional and network-level alterations in resting-state brain activity. The fronto-striatal-limbic circuits play a critical role in catastrophic-style emotion regulation in PD patients. Reduced FC within the default mode network and cerebellum-default mode network may signify a coordination anomaly in introspection and cognitive activities in PD. These findings complement the model of implicit emotion regulation in PD and suggest potential intervention targets.

Background: During the peak of the epidemic, hospitalized patients frequently encountered significant health risks and potentially life-threatening circumstances, including uncertainty regarding treatment and the potential for complications.

Objective: The present study aimed to explore the prevalence of post-traumatic stress disorder (PTSD) symptoms among hospitalized patients 3 months after discharge during the first peak of the epidemic, and the association of PTSD with disease-related characteristics.

Design: A single-center and full-sample follow-up study was conducted on COVID-19 patients from the Optical Valley Branch of Maternal and Child Hospital of Hubei Province, Wuhan, China. Data were collected during their hospitalization and 3 months after discharge.

Methods: PTSD symptoms were evaluated by primary care post-traumatic stress disorder (PC-PTSD), a total score of 3 or above was considered as clinically significant PTSD symptoms. Demographic and disease-related characteristics were collected to identify related associations with PTSD symptoms.

Results: A total of 903 patients completed the follow-up survey, yielding a response rate of 63.5%. A total of 212 (23.5%) of the patients were positive in PC-PTSD screening. Univariate regression analysis identified several factors correlated with PTSD symptoms, including female gender, younger age, a lower body mass index (BMI), preexisting sleep problems, bereavement due to COVID-19, a severe clinical diagnosis, the presence of three or more clinical symptoms at disease onset, and residual respiratory symptoms after discharge. Notably, in the multivariate regression analysis, experiencing three or more clinical symptoms at onset emerged as a robust predictor of PTSD symptoms (OR = 2.09, 95% CI: 1.48-2.95). An intriguing finding was that patients who underwent radiological assessment post-discharge reported a higher incidence of PTSD symptoms, whereas those who underwent re-testing for IgG or IgM antibodies exhibited a lower prevalence of PTSD symptoms.

Conclusion: Three months post-recovery, PTSD symptoms prevalence among COVID-19 patients was 23.5%. Those with three or more clinical symptoms at onset or residual respiratory symptoms post-discharge showed higher risk. These findings highlighted the long-term effect of COVID-19 on mental health, urging enhanced attention and interventions for survivors.

The purpose of this summary is to explain key findings from a study that included people with schizophrenia, as described in two separate articles (see the 'Further Information' section for more details). The study compared a new formulation of aripiprazole, given as an injection once every 2 months, with a once‑monthly injection of aripiprazole.