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.
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.
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