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1.
Neurol Sci ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38858237

ABSTRACT

BACKGROUND: Neurobrucellosis presents diverse clinical challenges and risks of long-term complications. OBJECTIVE: We aimed to assess the relationship between the duration of antibiotic therapy, clinical factors, and the outcome of neurobrucellosis with a case report combined with a systematic review of the literature. METHODS: We present a case of a 31 years-old man successfully treated at our Institution. We then searched Ovid MEDLINE, Embase and Scopus for articles that encompassed neurobrucellosis cases, duration of treatment, and outcome. The primary outcome was to assess an association between the duration of treatment and the risk of sequelae or relapses. Univariate, multivariate and sensitivity analysis were carried out to define which variables affect​ed​ the clinical outcome. Quality assessment was performed using a dedicated tool. RESULTS: A total of 123 studies were included, totaling 221 patients. Median duration of treatment was 4 months (IQR 3 - 6), 69% patients recovered without sequelae, 27% had sequelae. Additionally, five patients had a relapse, and 4 patients died. Multivariate analysis found that the duration of treatment, age, and the use of ceftriaxone were not associated with a higher risk of sequelae or relapses. A significant association was found for corticosteroids use (OR 0.39, 95% IC 0.16 - 0.96, p = 0.038), motor impairment (OR 0.29, 95% IC 0.14 - 0.62, p = 0.002), and hearing loss (OR 0.037, 95% IC 0.01 - 0.11, p < 0.001). CONCLUSIONS: This study highlights the variability in clinical presentations and treatment approaches for neurobrucellosis. Patients with factors indicating higher sequelae risk require meticulous follow-up.

2.
BMJ Ment Health ; 27(1)2024 May 20.
Article in English | MEDLINE | ID: mdl-38772637

ABSTRACT

BACKGROUND: New National Institute for Health and Care Excellence (NICE) guidance endorses the prescription of statins in larger population groups for the prevention of cardiovascular and cerebrovascular morbidity and mortality, especially in people with severe mental illness. However, the evidence base for their safety and risk/benefit balance in depression is not established. OBJECTIVES: This study aims to assess the real-world mortality and adverse events of statins in depressive disorders. METHODS: Population-based, nationwide (England), between-subject, cohort study. We used electronic health records (QResearch database) of people aged 18-100 years with first-episode depression, registered with English primary care practices over January 1998-August 2020 for 12(+) months, divided into statin users versus non-users.Primary safety outcomes included all-cause mortality and any adverse event measured at 2, 6 and 12 months. Multivariable logistic regression was employed to control for several potential confounders and calculate adjusted ORs (aORs) with 99% CIs. FINDINGS: From over 1 050 105 patients with depression (42.64% males, mean age 43.23±18.32 years), 21 384 (2.04%) died, while 707 111 (67.34%) experienced at least one adverse event during the 12-month follow-up. Statin use was associated with lower mortality over 12 months (range aOR2-12months 0.66-0.67, range 99% CI 0.60 to 0.73) and with lower adverse events over 6 months (range aOR2-6months 0.90-0.96, range 99% CI 0.91 to 0.99), but not at 1 year (aOR12months 0.99, 99% CI 0.96 to 1.03). No association with any other individual outcome measure (ie, any other neuropsychiatric symptoms) was identified. CONCLUSIONS: We found no evidence that statin use among people with depression increases mortality or other adverse events. CLINICAL IMPLICATIONS: Our findings support the safety of updated NICE guidelines for prescribing statins in people with depressive disorders.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Primary Health Care , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Female , Adult , Middle Aged , Primary Health Care/statistics & numerical data , Aged , Cohort Studies , Adolescent , Aged, 80 and over , Young Adult , England/epidemiology , Depressive Disorder/drug therapy , Depressive Disorder/mortality , Depressive Disorder/epidemiology , Depression/drug therapy , Depression/epidemiology
4.
Antimicrob Agents Chemother ; 68(4): e0002324, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38385700

ABSTRACT

Here, we describe the use of proactive therapeutic drug monitoring (TDM) to individualize the optimal timing of drug injections in 16 adult patients with chronic osteoarticular infections receiving a median of 7 injections of dalbavancin (up to 12 injections in 15 months). Dalbavancin injections were repeated at medians of 39-47 days, with infusion intervals ranging from 26 to 69 days. TDM can facilitates a precise, targeted use of dalbavancin for infections requiring prolonged treatments.


Subject(s)
Anti-Bacterial Agents , Teicoplanin , Teicoplanin/analogs & derivatives , Adult , Humans , Anti-Bacterial Agents/therapeutic use , Teicoplanin/therapeutic use
5.
BMC Med ; 21(1): 424, 2023 11 07.
Article in English | MEDLINE | ID: mdl-37936200

ABSTRACT

BACKGROUND: Antidepressants are licensed for use in depressive disorders, but non-response and poor adherence to treatment affect a considerable number of patients. Pre-clinical and clinical evidence suggest that statins can augment the effects of antidepressants. However, the acceptability and tolerability of combining statins with antidepressants are unclear, and their add-on efficacy has only been shown in small, short-term clinical trials. Observational data can provide complementary information about treatment effects on larger samples over longer follow-ups. In this study, we therefore assessed the real-world acceptability, tolerability, and efficacy of concomitant antidepressant and statin treatment in depression. METHODS: We conducted a population-based cohort study investigating QResearch primary care research database, which comprises the anonymised electronic healthcare records of 35 + million patients over 1574 English general practices. Patients aged 18-100 years, registered between January 1998 and August 2020, diagnosed with a new episode of depression, and commencing an antidepressant were included. Using a between-subject design, we identified two study groups: antidepressant + statin versus antidepressant-only prescriptions. Outcomes of interest included the following: antidepressant treatment discontinuations due to any cause (acceptability) and due to any adverse event (tolerability) and effects on depressive symptoms (efficacy) measured as response, remission, and change in depression score on the Patient Health Questionnaire-9. All outcomes were assessed at 2, 6, and 12 months using multivariable regression analyses, adjusted for relevant confounders, to calculate adjusted odds ratios (aORs) or mean differences (aMDs) with 99% confidence intervals (99% CIs). RESULTS: Compared to antidepressant-only (N 626,335), antidepressant + statin (N 46,482) was associated with higher antidepressant treatment acceptability (aOR2months 0.88, 99% CI 0.85 to 0.91; aOR6months 0.81, 99% CI 0.79 to 0.84; aOR12months 0.78, 99% CI 0.75 to 0.81) and tolerability (aOR2months 0.92, 99% CI 0.87 to 0.98; aOR6months 0.94, 99% CI 0.89 to 0.99, though not long term aOR12 months 1.02, 99% CI 0.97 to 1.06). Efficacy did not differ between groups (range aOR2-12 months 1.00 and 1.02 for response and remission, range aOR2-12 months - 0.01 and - 0.02 for change in depression score). CONCLUSIONS: On real-world data, there is a positive correlation between antidepressant treatment adherence and statin use, partly explained by fewer dropouts due to adverse events. The main limitation of our study is its observational design, which restricts the potential to make causal inferences.


Subject(s)
Antidepressive Agents , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Antidepressive Agents/therapeutic use , Cohort Studies , Depression/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Primary Health Care , Drug Therapy, Combination/adverse effects
6.
Chirurgia (Bucur) ; 118(4): 370-379, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37697999

ABSTRACT

Background: This study evaluates the feasibility, efficacy, the complications rate, and the long-term results of laparoscopic treatment of gastroesophageal reflux disease (GERD) at a dedicated center. Materials and Methods: From 01/11/1993 to 01/12/2019, we performed 620 fundoplication surgeries by laparoscopic approach according to Rossetti technique and 160 according to Toupet technique, totally 780 procedures for gastroesophageal reflux disease. The average duration of surgery was 40 minutes (range 19 - 160) for Rossetti fundoplication, 50 (range 30 - 180), and for Toupet 60 (range 45 - 190). All patients were investigated by upper digestive tract radiography, esophagogastroscopy, 24h computerized pH-metry, manometry and scintigraphy to assess esophageal clearance and gastric emptying times. In the 180 (23 %) patients with associated hiatal hernia, direct hiatoplasty was performed in 108 cases, and hiatoalloplasty in the remaining 72. Results: There were no cases of perioperative mortality; the morbidity rate was 6.28 %. We had 16.7 % long-term failures, requiring reintervention in 46 cases (6.5 %). Thirty patients (3.84 %) had to resume occasional 40 mg PPI therapy and 48 patients (6.15 %) had to resume 40 mg PPI therapy continuously. Manometry in these patients revealed lower esophageal sphincter tone between 10- and 16-mm hg with complete and coordinated relaxations. Of the 44 patients who underwent redo surgery 26 were reoperated to repackage a tighter plastic. Six patients required reoperation for dysphagia. Twelve paraesophageal hernias were recorded in the group of patients in whom only hiatoplasty without prosthesis was performed. In all cases, a hiatoplasty with prosthesis was repackaged laparoscopically. Conclusions: We emphasize the importance of accurate morphologic and functional evaluation of the esophagus preoperatively for selection of the most appropriate intervention and postoperatively for evaluation of the causes of failures. In the presence of hiatal hernia, it is always advisable to perform hiatoplasty with the placement of a prosthesis.


Subject(s)
Gastroesophageal Reflux , Hernia, Hiatal , Laparoscopy , Humans , Follow-Up Studies , Hernia, Hiatal/surgery , Quality of Life , Treatment Outcome , Gastroesophageal Reflux/surgery
8.
Obes Surg ; 33(9): 2749-2757, 2023 09.
Article in English | MEDLINE | ID: mdl-37466827

ABSTRACT

PURPOSE: Sleeve gastrectomy (SG) has become the most common bariatric procedure, but it is often characterized by the onset of postoperative gastroesophageal reflux disease (GERD). High-resolution manometry (HRM) is a useful tool to detect risk factors for GERD. The aim of this study was to evaluate preoperative manometric parameters as possible predictors of postoperative GERD. MATERIALS AND METHODS: This was a monocentric retrospective study. We analyzed 164 patients, with preoperative esophagitis/GERD symptoms who underwent preoperative HRM and were submitted to SG (July 2020-February 2022). RESULTS: Postoperative GERD was observed in 60 patients (36.6%): 41 of them (68%) already had preoperative GERD symptoms, whereas the remaining 19 patients (32%) developed postoperative symptoms. Female patients developed postoperative GERD in a significantly higher fraction of cases as compared to male patients (82% versus 18%; p < 0.001). DCI (distal contractile integral) was identified as the only HRM parameter correlating with the presence of GERD. Patients with DCI ≤ 1623 mmHg*cm*s developed postoperative GERD in 46% of cases (n = 43/94), as compared to 24% of cases (n = 17/70) among patients with DCI > 1623 mmHg*cm*s (p = 0.005). At multivariable analysis, female sex (OR 3.402, p = 0.002), preoperative GERD symptoms (OR 2.489, p = 0.013), and DCI ≤ 1623 mmHg*s*cm (OR 0.335, p = 0.003) were identified as independent determinants of postoperative GERD. CONCLUSION: All the patients with preoperative risk factors for reflux, such as GERD symptoms or esophagitis on EGDS (esophagogastroduodenoscopy), should be considered for an HRM. Moreover, when a DCI ≤ 1623 mmHg*s*cm is found, a bariatric procedure different from SG might be considered.


Subject(s)
Esophagitis , Gastroesophageal Reflux , Laparoscopy , Obesity, Morbid , Humans , Male , Female , Retrospective Studies , Obesity, Morbid/surgery , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/etiology , Gastroesophageal Reflux/surgery , Esophagitis/etiology , Manometry , Gastrectomy/methods , Laparoscopy/methods
9.
Transl Psychiatry ; 13(1): 253, 2023 07 12.
Article in English | MEDLINE | ID: mdl-37438361

ABSTRACT

Statins are commonly prescribed medications widely investigated for their potential actions on the brain and mental health. Pre-clinical and clinical evidence suggests that statins may play a role in the treatment of depressive disorders, but only the latter has been systematically assessed. Thus, the physiopathological mechanisms underlying statins' putative antidepressant or depressogenic effects have not been established. This review aims to gather available evidence from mechanistic studies to strengthen the pharmacological basis for repurposing statins in depression. We used a broad, well-validated search strategy over three major databases (Pubmed/MEDLINE, Embase, PsychINFO) to retrieve any mechanistic study investigating statins' effects on depression. The systematic search yielded 8068 records, which were narrowed down to 77 relevant papers. The selected studies (some dealing with more than one bodily system) described several neuropsychopharmacological (44 studies), endocrine-metabolic (17 studies), cardiovascular (6 studies) and immunological (15 studies) mechanisms potentially contributing to the effects of statins on mood. Numerous articles highlighted the beneficial effect of statins on depression, particularly through positive actions on serotonergic neurotransmission, neurogenesis and neuroplasticity, hypothalamic-pituitary axis regulation and modulation of inflammation. The role of other mechanisms, especially the association between statins, lipid metabolism and worsening of depressive symptoms, appears more controversial. Overall, most mechanistic evidence supports an antidepressant activity for statins, likely mediated by a variety of intertwined processes involving several bodily systems. Further research in this area can benefit from measuring relevant biomarkers to inform the selection of patients most likely to respond to statins' antidepressant effects while also improving our understanding of the physiopathological basis of depression.


Subject(s)
Depression , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Depression/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Affect , Brain , Databases, Factual
10.
BJPsych Open ; 9(4): e110, 2023 Jun 14.
Article in English | MEDLINE | ID: mdl-37313755

ABSTRACT

BACKGROUND: Evidence suggests inflammation may be a key mechanism by which psychosocial stress, including loneliness, predisposes to depression. Observational and clinical studies have suggested simvastatin, with its anti-inflammatory properties, may have a potential use in the treatment of depression. Previous experimental medicine trials investigating 7-day use of statins showed conflicting results, with simvastatin displaying a more positive effect on emotional processing compared with atorvastatin. It is possible that statins require longer administration in predisposed individuals before showing the expected positive effects on emotional processing. AIMS: Here, we aim to test the neuropsychological effects of 28-day simvastatin administration versus placebo, in healthy volunteers at risk for depression owing to loneliness. METHOD: This is a remote experimental medicine study. One hundred participants across the UK will be recruited and randomised to either 28-day 20 mg simvastatin or placebo in a double-blind fashion. Before and after administration, participants will complete an online testing session involving tasks of emotional processing and reward learning, processes related to vulnerability to depression. Working memory will also be assessed and waking salivary cortisol samples will be collected. The primary outcome will be accuracy in identifying emotions in a facial expression recognition task, comparing the two groups across time.

11.
Updates Surg ; 75(4): 959-965, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36849646

ABSTRACT

INTRODUCTION: Laparoscopic sleeve gastrectomy (SG) has rapidly become one of the most commonly performed procedures in bariatric surgery. Weight regain and insufficient weight loss are the most common causes for surgical failure. Re-sleeve gastrectomy (ReSG) can represent an option when there is evidence of a dilated gastric tube. OBJECTIVES: The aim of the study is to evaluate safety, efficacy and rate of gastro-esophageal reflux disease (GERD) after ReSG in one of the largest series present in literature with long-term follow up. METHODS AND STUDY DESIGN: Retrospective study design. From February 2010 to August 2018, 102 patients underwent ReSG at our Centre. We divided patients into two groups, according to the main reason for surgical failure: insufficient weight loss or progressive weight regain. RESULTS: One hundred-two patients (78 women, 24 men) with BMI 38 ± 6 kg/m2 underwent ReSG (mean age 44 years). Rate of postoperative complications was 3.9% (4/102). After a mean follow-up of 55 months, mean BMI decreased to 30,4 kg/m2 and the mean percentage of excess weight loss (%EWL) was 51 ± 38.6. Symptoms of GERD were present in 35/102 patients (34.3%) and the need for a new operation occurred in six patients. Forty-five patients were submitted to ReSG for progressive weight regain (group A) and 57 for insufficient weight loss (group B). No differences were found in terms of postoperative BMI and %EWL. CONCLUSION: ReSG is a feasible procedure after primary SG failure in selected patients, but its efficacy in reducing the BMI under 30 kg/m2 is still unclear. In addition, over 30% of patients suffer from long-term gastro-esophageal reflux.


Subject(s)
Gastroesophageal Reflux , Laparoscopy , Obesity, Morbid , Male , Humans , Female , Adult , Follow-Up Studies , Retrospective Studies , Reoperation/adverse effects , Laparoscopy/methods , Gastroesophageal Reflux/epidemiology , Gastroesophageal Reflux/surgery , Gastroesophageal Reflux/etiology , Gastrectomy/methods , Weight Loss , Weight Gain , Obesity, Morbid/surgery , Obesity, Morbid/complications , Treatment Outcome
12.
J Laparoendosc Adv Surg Tech A ; 33(1): 44-51, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35675688

ABSTRACT

Background: Laparoscopic sleeve gastrectomy (LSG) is associated with the long-term development of gastroesophageal reflux disease (GERD). Recent studies on LSG with fundoplication showed a lower rate of postoperative GERD than LSG alone; however, there is a lack of objective instrumental data in the literature. This study aimed to evaluate whether and how fundoplication associated with Sleeve Gastrectomy affects the esophagogastric physiology. Materials and Methods: This prospective observational study included 20 patients with morbid obesity, GERD, and lower esophageal sphincter (LES) hypotonia. All the patients underwent LSG with Rossetti fundoplication. High-resolution manometry was performed pre- and postoperatively. All the patients completed the 6 months follow-up. Results: The fundoplication increased LES tone in all patients. The increase in the LES tone was statistically significant (330% increase). The integrated relaxation pressure and the distal contractile integral both increased accordingly, indicating an increased esophageal effort to pass through the modified esophagogastric junction. Conclusion: Rossetti fundoplication associated with LSG increased LES tone and decreased the chance of developing long-term GERD after LSG.


Subject(s)
Gastroesophageal Reflux , Laparoscopy , Obesity, Morbid , Humans , Esophageal Sphincter, Lower/surgery , Fundoplication , Gastroesophageal Reflux/surgery , Gastrectomy , Manometry , Obesity, Morbid/surgery , Treatment Outcome
13.
Antibiotics (Basel) ; 13(1)2023 Dec 24.
Article in English | MEDLINE | ID: mdl-38247579

ABSTRACT

Dalbavancin is a long-acting lipoglycopeptide that is registered for the treatment of acute bacterial skin and skin structure infections, and it is also increasingly used for infections that require prolonged antibiotic treatment. Here, we present the results from the first 2 years of a service set up in December 2021 for the therapeutic drug monitoring (TDM) of dalbavancin in clinical settings. In particular, we compared the trough concentration (Cmin) to maximum concentration (Cmax) in patients with osteoarticular infections receiving prolonged treatment with dalbavancin. Log-linear regression models were used to estimate the timing of dalbavancin administration with the goal of maintaining Cmin concentrations of >8 mg/L in the two TDM-based strategies. From December 2021 to November 2023, 366 TDMs of dalbavancin from 81 patients were performed. The Cmin and Cmax concentrations of dalbavancin ranged from 4.1 to 70.5 mg/L and from 74.9 to 995.6 mg/L, respectively. With log-linear regression models, we estimated that each injection should be administered every 42-48 days to maintain the Cmin concentrations. Out of the 81 patients, 37 received at least three doses of dalbavancin for the treatment of osteoarticular infections. Despite there being no significant differences in the days of dalbavancin treatment (130 ± 97 versus 106 ± 102 days), the patients in the Cmax-based TDM group received a significantly lower number of dalbavancin injections (5.2 ± 1.8 versus 7.3 ± 2.6 injections, p = 0.005), and they were administered over a longer period of time (40 ± 10 versus 29 ± 14 days, p = 0.013) than in the Cmin-based TDM group. In conclusion, Cmax-based TDM was associated with a significant reduction in the inter-individual variability of dalbavancin concentrations and lower drug dosing frequency than those of Cmin-based TDM. This approach could, therefore, favor a more rational and targeted use of dalbavancin in patients requiring prolonged treatment.

14.
Surg Obes Relat Dis ; 18(10): 1199-1205, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35760673

ABSTRACT

BACKGROUND: Gastroesophageal reflux disease (GERD), including erosive esophagitis, is highly prevalent in the obese population. Barrett's esophagus is the consequence of untreated GERD. Laparoscopic sleeve gastrectomy is one of the most frequently performed bariatric procedures. This study presents results after 5 years of follow-up of combined LSG and Rossetti fundoplication for the treatment of GERD, esophagitis, and Barrett's esophagus in patients with morbid obesity. OBJECTIVE: To evaluate long-term results after sleeve gastrectomy with Rossetti fundoplication. SETTING: Public university hospital in Italy. METHODS: Since January 2015, more than 450 patients with obesity underwent sleeve gastrectomy with a Rossetti fundoplication procedure as part of prospective studies underway at our center performed by 4 different expert bariatric surgeons. Currently, 127 patients have a follow-up of 5 years or more. RESULTS: Mean patient age was 42.9 ± 10.3 years, and mean body mass index was 42.4 ± 6.1 kg/m2. In total, 74.8% of patients were experiencing GERD before surgery. In 29 of 127 patients (22.8%), preoperative gastroscopy showed signs of esophagitis and/or Barrett's esophagus. In particular, 23 of 127 patients (18.1%) had grade A esophagitis, 2 of 127 (1.6%) had grade B, 2 of 127 (1.6%) had grade C, and 2 of 127 (1.6%) had Barrett's esophagus. Mean operative time was 51 ± 21 minutes. No intraoperative complications or conversions were reported. A regular postoperative course was seen in 91.3% of patients. Sixty months after surgery, more than 95% of patients did not experience any reflux symptoms. Percent total weight loss at follow-up was comparable with that with sleeve gastrectomy. Endoscopic follow-up demonstrated improvement of esophagitis lesions (including Barrett's esophagus) present in the preoperative setting. CONCLUSION: Laparoscopic sleeve gastrectomy with Rossetti fundoplication is well tolerated, feasible, and safe in patients with obesity, providing adequate weight loss results and complete resolution of clinical signs of GERD. We have recorded an improvement in esophagitis lesions present at preoperative gastroscopy and complete resolution of Barrett's esophagus within 5 years of follow-up.


Subject(s)
Barrett Esophagus , Esophagitis , Gastroesophageal Reflux , Laparoscopy , Obesity, Morbid , Adult , Barrett Esophagus/diagnosis , Barrett Esophagus/surgery , Esophagitis/etiology , Esophagitis/surgery , Follow-Up Studies , Fundoplication/methods , Gastrectomy/methods , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/surgery , Humans , Laparoscopy/methods , Middle Aged , Obesity, Morbid/complications , Prospective Studies , Weight Loss
15.
Psychopharmacology (Berl) ; 239(8): 2635-2645, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35511258

ABSTRACT

RATIONALE: Clinical studies suggest that the highly lipophilic, anti-inflammatory molecule, simvastatin, might be an ideal candidate for drug repurposing in the treatment of depression. The neuropsychological effects of simvastatin are not known, but their ascertainment would have significant translational value about simvastatin's influence on mood and cognition. OBJECTIVES: We aimed to investigate the effects of simvastatin on a battery of psychological tests and inflammatory markers in healthy volunteers. METHODS: Fifty-three healthy subjects were randomly assigned to 7 days of either simvastatin (N = 27) or sucrose-based placebo (N = 26) given in a double-blind fashion. Then, participants were administered questionnaires measuring subjective rates of mood and anxiety, and a battery of tasks assessing emotional processing, reward learning, and verbal memory. Blood samples for C-reactive protein were also collected. RESULTS: Compared to placebo, participants on simvastatin showed a higher number of positively valenced intrusions in the emotional recall task (F1,51 = 4.99, p = 0.03), but also an increase in anxiety scores (F1,51 = 5.37, p = 0.02). An exploratory analysis of the females' subgroup (N = 27) showed lower number of misclassifications as sad facial expression in the simvastatin arm (F1,25 = 6.60, p = 0.02). No further statistically significant changes could be observed on any of the other outcomes measured. CONCLUSIONS: We found limited evidence that 7-day simvastatin use in healthy volunteer induces a positive emotional bias while also being associated with an increase in anxiety, potentially reflecting the early effects of antidepressants in clinical practice. Such effect might be more evident in female subjects. Different drug dosages, treatment lengths, and sample selection need consideration in further experimental medicine and clinical studies. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04652089.


Subject(s)
Biomedical Research , Simvastatin , Double-Blind Method , Female , Healthy Volunteers , Humans , Inflammation/drug therapy , Reward , Simvastatin/pharmacology , Verbal Learning
16.
J Affect Disord ; 311: 336-343, 2022 08 15.
Article in English | MEDLINE | ID: mdl-35618167

ABSTRACT

INTRODUCTION: Statins have been proposed as a strategy for treating depression, but their benefit in the absence of concurrent antidepressant treatment is unclear. This meta-analysis investigated the antidepressant effects of statin monotherapy in the general population. METHODS: We conducted a literature search of randomised controlled trials using any statin monotherapy versus any control condition for depressive symptoms. Our primary efficacy outcome was the mean value on any standardised scale for depression at study endpoint. We also measured efficacy at three further timepoints (<6 months, 6-12 months, >12 months), as well as acceptability, tolerability, and safety. Respectively, continuous and dichotomous outcomes were computed using standardised mean difference (SMD) or relative risk (RR) with 95% confidence intervals (CI) using a random-effect model. RESULTS: Pooled analyses did not show that statin monotherapy improves depressive symptoms at endpoint (N = 2712 SMD = -0.18; 95% CI = -0.41 to 0.04), nor at any other specific timepoint. No difference between statins and control was identified for any of the other outcome measures. DISCUSSION: These results differ from those of previous meta-analyses and, compounded by more recently available evidence, suggest that statins may not have intrinsic antidepressant properties, but may be useful for the management of depression in add-on to antidepressants. LIMITATIONS: Data from heterogeneous populations and using different statins were pooled, though several sensitivity and subgroup analyses were performed to account for that. PROSPERO registration: CRD42022306653. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=306653.


Subject(s)
Depression , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Antidepressive Agents/adverse effects , Depression/drug therapy , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects
18.
Int Rev Psychiatry ; 34(7-8): 699-714, 2022.
Article in English | MEDLINE | ID: mdl-36786109

ABSTRACT

Depression has a large burden, but the development of new drugs for its treatment has proved difficult. Progresses in neuroscience have highlighted several physiopathological pathways, notably inflammatory and metabolic ones, likely involved in the genesis of depressive symptoms. A novel strategy proposes to repurpose established medical treatments of known safety and to investigate their potential antidepressant activity. Among numerous candidates, growing evidence suggests that statins may have a positive role in the treatment of depressive disorders, although some have raised concerns about possible depressogenic effects of these widely prescribed medications. This narrative review summarises relevant findings from translational studies implicating many interconnected neurobiological and neuropsychological, cardiovascular, endocrine-metabolic, and immunological mechanisms by which statins could influence mood. Also, the most recent clinical investigations on the effects of statins in depression are presented. Overall, the use of statins for the treatment of depressive symptoms cannot be recommended based on the available literature, though this might change as several larger, methodologically robust studies are being conducted. Nevertheless, statins can already be acknowledged as a driver of innovation in mental health, as they provide a novel perspective to the physical health of people with depression and for the development of more precise antidepressant treatments.


Subject(s)
Depression , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Depression/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Mental Health , Antidepressive Agents/adverse effects , Affect
19.
J Psychopharmacol ; 35(12): 1479-1487, 2021 12.
Article in English | MEDLINE | ID: mdl-34872404

ABSTRACT

BACKGROUND: Growing evidence from clinical trials and epidemiological studies suggests that statins can have clinically significant antidepressant effects, potentially related to anti-inflammatory action on several neurobiological structures. However, the underlying neuropsychological mechanisms of these effects remain unexplored. AIMS: In this experimental medicine trial, we investigated the 7-day effects of the lipophilic statin, atorvastatin on a battery of neuropsychological tests and inflammation in healthy volunteers. METHODS: Fifty healthy volunteers were randomised to either 7 days of atorvastatin 20 mg or placebo in a double-blind design. Participants were assessed with psychological questionnaires and a battery of well-validated behavioural tasks assessing emotional processing, which is sensitive to putative antidepressant effects, reward learning and verbal memory, as well as the inflammatory marker, C-reactive protein. RESULTS: Compared to placebo, 7-day atorvastatin increased the recognition (p = 0.006), discriminability (p = 0.03) and misclassifications (p = 0.04) of fearful facial expression, independently from subjective states of mood and anxiety, and C-reactive protein levels. Otherwise, atorvastatin did not significantly affect any other psychological and behavioural measure, nor peripheral C-reactive protein. CONCLUSIONS: Our results reveal for the first time the early influence of atorvastatin on emotional cognition by increasing the processing of anxiety-related stimuli (i.e. increased recognition, discriminability and misclassifications of fearful facial expression) in healthy volunteers, in the absence of more general effects on negative affective bias. Further studies exploring the effects of statins in depressed patients, especially with raised inflammatory markers, may clarify this finding and inform future clinical trials.


Subject(s)
Atorvastatin/pharmacology , Emotions/drug effects , Facial Recognition/drug effects , Fear/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Inflammation/drug therapy , Reward , Social Perception/drug effects , Verbal Learning/drug effects , Adolescent , Adult , Atorvastatin/administration & dosage , Biomedical Research , C-Reactive Protein/drug effects , Depression/drug therapy , Double-Blind Method , Female , Healthy Volunteers , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Inflammation/blood , Male , Middle Aged , Young Adult
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