The paliperidone palmitate 3-month (PP3M) formulation offers an extended dosing interval compared to the 1-month (PP1M) formulation. However, data on the comparative side effect profiles of PP1M versus PP3M in real-world settings remain limited. This study aimed to compare the side effect profiles in patients with schizophrenia receiving PP1M and those who switched from PP1M to PP3M.
Of 473 patients with schizophrenia screened, 132 received long-acting injectable antipsychotics; 67 initiated PP1M, of whom 43 subsequently converted to PP3M and had evaluable data at both time points. The primary analysis used a within-patient mirror-image design (PP1M month-4 vs PP3M month-4). Side effects were assessed using the UKU Side Effect Rating Scale, and symptom severity was evaluated with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms, at 4 months after PP1M initiation and 4 months after PP3M switch.
UKU side-effect profiles were broadly similar after conversion to PP3M, with no increase in the UKU total score. The most frequent side effects for both formulations were increased fatigability, hypokinesia, weight gain, and diminished sexual desire. The frequency of side effects remained mostly stable, with constipation showing a significant decrease after switching. Side effects were more prevalent in patients with schizophrenia using multiple antipsychotics compared to monotherapy.
In this within-patient cohort stabilized on PP1M, conversion to PP3M was not associated with an increase in overall UKU side-effect burden. Selecting the appropriate dose before switching and preferring monotherapy may enhance treatment comfort. These results may help guide clinicians in selecting long-acting injectable antipsychotics in practice.
Anxiety is common in patients receiving end-of-life care and significantly impacts their quality of life. However, pharmacological management remains challenging due to complex clinical presentations and potential side effects, emphasizing the need for systematically reviewing existing treatments. Here we aim to systematically evaluate the efficacy and safety of pharmacological treatments for anxiety in end-of-life care.
Systematic review following PRISMA guidelines, prospectively registered in PROSPERO (CRD42024556913). Comprehensive searches were performed in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. Eligible studies included adults receiving end-of-life care and evaluated pharmacological interventions targeting anxiety.
Five studies met inclusion criteria: two assessing benzodiazepines combined with opioids and three evaluating psilocybin. Both benzodiazepine-opioid combinations and psilocybin reduced anxiety symptoms. Psilocybin studies reported rapid and sustained anxiety relief, with approximately 60%–80% of participants experiencing clinically significant improvements. Both treatment categories showed good tolerability without serious adverse events. However, the evidence base was limited by small sample sizes and narrow study contexts.
Benzodiazepine-opioid combinations and psilocybin show promise for anxiety relief in end-of-life patients. Nevertheless, limited high-quality evidence highlights an important research gap. Further robust clinical trials are needed to confirm these findings and guide clinical practice in palliative care.
This double-blind positive-controlled study investigated the potential for the aroma of a novel blend of essential oils, Genius to enhance cognitive performance and mood in healthy adults, and whether any such benefits might be related to changes in cerebrovascular oxygenation measured using Near Infra-Red Spectroscopy. Ninety participants (61 female) were pseudo-randomly allocated to achieve a gender balance across three experimental groups: Genius aroma, Sage aroma (positive control) or no aroma (control). All participants completed mood questionnaires after completing a range of cognitive tasks whilst wearing a Near Infra-Red Spectroscopy headband. Multivariate and subsequent univariate data analysis revealed significant enhancements to memory and executive function tasks in the Genius and sage aroma conditions compared to no aroma with larger effects noted for the Genius blend. Furthermore, the novel blend outperformed the aroma of pure sage and also left participants feeling significantly more alert and less fatigued at the end of the testing session. Near Infra-Red Spectroscopy data indicated that both sage and Genius blend enhanced metabolism during task performance with a greater impact from the Genius aroma. Although suggestive of a mechanism underpinning the enhancements observed no correlations were found between the Near Infra-Red Spectroscopy signals and cognitive performance. This study strengthens the evidence base for the beneficial effects of essential oil aroma inhalation for cognitive performance, however the underlying mechanisms remain elusive.
C-C motif chemokine ligand 5 (CCL5) and fibroblast growth factor 2 (FGF2) have been increasingly linked to neuroinflammation. This study evaluated the impact of escitalopram on serum CCL5 and FGF2 levels in patients with generalised anxiety disorder (GAD).
Thirty patients (18–50 years) with GAD diagnosed by DSM-5 criteria, and 30 healthy controls were included. All GAD patients received escitalopram and were followed up for 12 weeks. Serum CCL5 and FGF2 levels were measured before and after escitalopram treatment in GAD patients, with a baseline measurement in healthy controls using ELISA.
We found that serum CCL5 levels were significantly increased (p = 0.001) in GAD patients compared to healthy controls and remained higher after treatment without any significant change. However, serum FGF2 levels were comparable and did not differ significantly between healthy controls and GAD patients before treatment, and increased significantly (p = 0.011) after escitalopram treatment in GAD patients.
In GAD patients, serum levels of CCL5 remained elevated and FGF2 increased significantly post-treatment with escitalopram. This suggests that escitalopram could exert a partial immunomodulatory effect on CCL5 and FGF2, thus modulating inflammation-driven mechanisms of GAD. Future research in larger populations and longer follow-ups is needed to further examine these findings.
Scopolamine disrupts cholinergic mechanisms via nonspecific muscarinic antagonism. Centrally, excitatory neocortical innervations are antagonised causing spectral electroencephalography (EEG) changes and cognitive impairment. Peripherally, parasympathetic control of heart rate variability (HRV) is disrupted, although acute HRV effects of scopolamine are not well-defined.
Forty adults with depression received scopolamine hydrobromide (N = 24, 4–6 μg/kg) or glycopyrronium bromide (N = 16, 4–6 μg/kg) infusions. Twelve healthy adults received scopolamine (4–6 μg/kg) infusions. EEG and electrocardiography were recorded across 4 hours post-infusion. EEG spectral, aperiodic, Lempel Ziv complexity (LZC), and microstates analyses were performed. Electrocardiographic HRV metric: proportion of high frequency power (pHF) was calculated and modelled via pharmacokinetic-pharmacodynamic models to ascertain the HRV concentration-effect relationship.
Scopolamine increased delta power between 0.5 and 3.5 h (at 35 min: t = 3.6, p = 0.002). At 3 hours post-infusion, scopolamine increased aperiodic slope (t = −3.4, p = 0.047) and offset (t = −3.93, p = 0.003) parameters, reduced LZC (t = −4.5, p = 2 × 10−4), and microstate D mean duration (t = −3.0, p = 0.039). EEG metrics correlated with drowsiness and alcohol-like stimulant ratings. Peripherally, scopolamine reduced HRV, with two-compartment pharmacokinetic models describing a delayed pHF effect via an effect compartment.
These effects corresponded to increased drowsiness, reduced excitation-inhibition ratio, and reduced HRV—implicating central and peripheral muscarinic mechanisms reminiscent of Alzheimer's-like cholinergic disruption.
anzctr.org.au identifier: ACTRN12619000569101 and ACTRN12622000228785.
Stress from daily psychosocial challenges is a significant health concern with limited pharmacological treatment options. Psychosocial stress triggers distinct responses in the autonomic and central nervous systems, measurable via heart rate variability (HRV) and electroencephalogram (EEG). This post hoc analysis of clinical trial data explores the impact of the anti-stress medication Neurexan (Nx4) on HRV and EEG signals, and their correlation in a resting state following acute psychosocial stress induction.
Data from the NEURIM trial (NCT02602275), a randomized, placebo-controlled, double-blind, cross-over study, were utilized. Participants received Nx4 before exposure to ScanSTRESS, a psychosocial stress paradigm. EEG and photoplethysmogram data were collected at rest before and after stress exposure. Stress responsivity under both placebo and Nx4 conditions was evaluated through HRV and EEG signals.
Psychosocial stress altered HRV parameters (increased LF/HF ratio, elevated Baevsky's Stress Index, reduced RMSSD) and EEG activity (decreased aperiodic offset, increased alpha power). Nx4 significantly mitigated stress-induced changes in LF/HF ratio, Baevsky's Stress Index, and aperiodic offset. A significant correlation was observed between Nx4 effects on HRV and EEG activity.
Nx4 attenuates peripheral and central physiological stress responses, suggesting a comprehensive approach to mitigating stress responses in daily life.
Loss of function mutations in the WFS1 gene cause Wolfram syndrome, which is characterized by juvenile-onset diabetes mellitus, diabetes insipidus, neurodegeneration, hearing loss and optic nerve atrophy. Psychiatric symptoms, including major depression and suicidal behavior, are common in this disorder. WFS1 mutations induce this condition through altering interactions between the endoplasmic reticulum and mitochondria, resulting in diminished Ca2+ import that leads to mitochondrial dysfunction. Quite recently, it was shown that such impaired Ca2+ transport could be restored by the experimental σ1 receptor agonist PRE084. In animal models of Wolfram syndrome, this compound restored the behavioral phenotype. Based on these previous data, we propose that Wolfram syndrome may serve as a mechanistically informative model for exploring σ1 receptor modulation, mitochondrial dysfunction, and affective symptoms. This proposal is based on four arguments. Firstly, the R-enantiomer of ketamine exhibits largely selective binding to the σ1 receptor as an agonist. Secondly, R-ketamine and other σ1 agonists display antidepressant-like activity in rodent depression models. Thirdly, while both S- and R-ketamine hold potential for reducing suicidal behavior, the latter is likely to have a lower potential for abuse and fewer side effects. Fourth, Wolfram syndrome is characterized by mitochondrial dysfunction, which has also been linked to depression.
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