Therapeutic Advances in Psychopharmacology最新文献

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.

The purpose of this summary is to explain key findings from a study that included people with bipolar I disorder, 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.

Background: Optimal use of lithium involves adjustment of the dose, to keep the plasma level within the narrow, recommended range. Brand-specific prescribing has long been considered critical to achieving this aim, but this is a convention based on very limited data.

Objectives: To explore the effect of selected demographic and clinical factors on the relationship between lithium dose and plasma level and determine whether there is an independent effect of lithium brand.

Design: Analysis of clinical audit data collected in 2023 as part of a quality improvement programme addressing the use of lithium, conducted by the Prescribing Observatory for Mental Health.

Methods: Data were collected from clinical records using a bespoke proforma, submitted online and analysed using SPSS.

Results: Data were submitted for 4405 patients who had been prescribed solid-dosage formulations of lithium for more than a year. Priadel^® was prescribed for 3722 (84%) of these patients, Camcolit^® for 112 (2.5%) and the prescription was written generically for 554 (12.5%). Compared with Priadel, where Camcolit was prescribed, the mean daily dose was 10% higher and the mean plasma lithium level was 11% higher. A multivariable analysis was conducted to explore the relationship between selected clinical variables and maintenance lithium dose. This found that in 4213 patients whose most recent plasma lithium level was between 0.3 and 1.19 mmol/L, the variables age, sex, ethnicity, psychiatric diagnosis and the severity of chronic kidney disease were independently associated with dose while the brand of lithium prescribed was not.

Conclusion: Our findings replicate those of previous studies with respect to the demographic and clinical variables that can be expected to influence lithium dosage in routine clinical practice. This reinforces the need to titrate the dosage for each individual patient, to achieve and maintain the target plasma level. However, the findings suggest that the Priadel and Camcolit brands of lithium are essentially interchangeable.

Background: Repetitive transcranial magnetic stimulation (rTMS) showed potentially beneficial effects for the treatment of post-traumatic stress disorder (PTSD). Low-frequency (LF) rTMS decreases neuronal excitability and may have better safety compared to high-frequency (HF) rTMS. However, there lacks meta-analysis specifically focusing on LF rTMS.

Objectives: To specifically explore the efficacy and safety of LF rTMS for treating PTSD.

Methods: Databases including PubMed, EMBASE, MEDLINE, and Web of Science were systematically searched from inception to October 17, 2023. Both randomized controlled trials (RCTs) and open trials of LF rTMS on PTSD were included, and we additionally included RCTs comparing HF rTMS and sham treatment on PTSD. First, we qualitatively summarized parameters of LF rTMS treatment; then, we extracted data from the LF rTMS treatment subgroups of these studies to examine its effect size and potential influencing factors; third, we compared the effect sizes among LF rTMS, HF rTMS and sham treatment through network meta-analysis of RCTs.

Results: In all, 15 studies with a sample size of 542 participants were included. The overall effect size for LF rTMS as a treatment for PTSD was found as Hedges' g = 1.02 (95% CI (0.56, 1.47)). Meta-regression analysis did not reveal any influencing factors. Network meta-analysis showed that compared to sham treatment, only HF rTMS on the right dorsolateral prefrontal cortex (DLPFC) demonstrated a significant advantage in ameliorating PTSD symptoms, while LF rTMS on the right DLPFC showed a trend toward advantage, but the difference was not significant.

Conclusion: The current literature shows LF rTMS has effect in treating PTSD caused by various traumatic events. However, present limited number of RCT studies only showed LF rTMS to have a trend of advantage compared to sham treatment in treating PTSD caused by external traumatic events. In the future, more RCTs are needed to be made to confirm the efficacy of LF rTMS. Additionally, studies are required to elucidate the underlying mechanism in order to further improve its efficacy in different traumatic populations.

Prospero registration number: CRD42023470169.

One of the most important challenges in the management of patients with schizophrenia is to ensure adherence to antipsychotic treatment. The contribution of long-acting injectables (LAI) is undeniable in this matter, but there are still some unmet medical needs not covered by these drugs (e.g. quick onset of action for patients with acute exacerbation of schizophrenia). This article summarises the pharmacokinetics, efficacy and safety of Risperidone ISM (in situ microparticles). The aim of this review is to provide information about the potential uses of this new LAI formulation of risperidone for the treatment of schizophrenia, contextualising and diving into the published evidence. Risperidone ISM shows a rapid release which allows achieving within 12 h risperidone active moiety levels similar to those observed in the steady-state for oral risperidone treatment, achieving a mean average concentration of 38.63 ng/mL. The plasma concentration of active moiety achieved by Risperidone ISM comes with a predictable dopamine D2 receptor occupancy above 65% throughout the 28-day dosing period, which is accepted as a threshold for the efficacy of the antipsychotic treatment. This can be associated with the positive efficacy findings throughout its clinical development. In the short term, it provides an early and progressive reduction of symptoms in adult patients with acute exacerbation of schizophrenia without the need for loading doses or oral risperidone supplementation, which could contribute to reinforcing the therapeutic alliance between the patient and the psychiatrist. In addition, long-term treatment was effective, safe and well tolerated regardless of the initial disease severity or whether patients were previously treated with Risperidone ISM during an acute exacerbation or switched from stable doses of oral risperidone. Improvement and maintenance of personal and social functioning and health-related quality of life were observed in each setting, respectively. All these findings endorse Risperidone ISM as a useful and valuable treatment for the acute and maintenance management of patients with schizophrenia.