Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis.

BACKGROUND: Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms has not been quantified. An estimate of antidepressant discontinuation symptoms incidence could inform patients and clinicians in the discontinuation of treatment, and provide useful information to researchers in antidepressant treatments. We aimed to assess the incidence of antidepressant discontinuation symptoms in patients discontinuing both antidepressants and placebo in the published literature. METHODS: We systematically searched Medline, EMBASE, and CENTRAL from database inception until Oct 13, 2022 for randomised controlled trials (RCTs), other controlled trials, and observational studies assessing the incidence of antidepressant discontinuation symptoms. To be included, studies must have investigated cessation or tapering of an established antidepressant drug (excluding antipsychotics, lithium, or thyroxine) or placebo in participants with any mental, behavioural, or neurodevelopmental disorder. We excluded studies in neonates, and those using antidepressants for physical conditions such as pain syndromes due to organic disease. After study selection, summary data extraction, and risk of bias evaluation, data were pooled in random-effects meta-analyses. The main outcome was the incidence of antidepressant discontinuation symptoms after discontinuation of antidepressants or placebo. We also analysed the incidence of severe discontinuation symptoms. Sensitivity and meta-regression analyses tested a selection of methodological variables. FINDINGS: From 6095 articles screened, 79 studies (44 RCTs and 35 observational studies) covering 21 002 patients were selected (72% female, 28% male, mean age 45 years [range 19·6-64·5]). Data on ethnicity were not consistently reported. 16 532 patients discontinued from an antidepressant, and 4470 patients discontinued from placebo. Incidence of at least one antidepressant discontinuation symptom was 0·31 (95% CI 0·27-0·35) in 62 study groups after discontinuation of antidepressants, and 0·17 (0·14-0·21) in 22 study groups after discontinuation of placebo. Between antidepressant and placebo groups of included RCTs, the summary difference in incidence was 0·08 [0·04-0·12]. The incidence of severe antidepressant discontinuation symptoms after discontinuation of an antidepressant was 0·028 (0·014-0·057) compared with 0·006 (0·002-0·013) after discontinuation of placebo. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms. Heterogeneity of results was substantial. INTERPRETATION: Considering non-specific effects, as evidenced in placebo groups, the incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication. Subgroup analyses and heterogeneity figures point to factors not accounted for by diagnosis, medication, or trial-related characteristics, and might indicate subjective factors on the part of investigators, patients, or both. Residual or re-emerging psychopathology needs to be considered when interpreting the results, but our findings can inform clinicians and patients about the probable extent of antidepressant discontinuation symptoms without causing undue alarm. FUNDING: None.

The use of honey in button battery ingestions: a systematic review.

Background: Button battery (BB) ingestions may cause severe and possibly fatal complications, especially if the battery is located in the esophagus. The application of oral honey has recently been proposed by the National Capital Poison Center in the USA and in an ESPGHAN position paper in Europe, but clinical trials and experimental studies are limited. The goal of this systematic review was to analyze the evidence for this approach. Materials and methods: A systematic review of clinical trials and experimental studies on the oral application of honey after BB ingestion in children was performed. Inclusion criteria according to the PICO format were patient age 0-18 years, ingestion of BB, oral administration of honey or other substances, all in vivo and in vitro studies, as well as reported complication rate, esophageal injury, and mortality. A manual search in the databases MEDLINE, Web of Science and Cochrane was performed to identify relevant search terms to form the following queries and to construct the extensive search. Furthermore, the search was extended by using snowballing on the reports reference lists. The review is registered at Research Registry. The identifying number is reviewregistry1581. Results: We found four publications that investigated the effects of honey after button battery ingestion. Three of these presented experimental in vitro and in vivo results and one reported a clinical retrospective study of 8 patients. Conclusion: Follow up studies are required to further elucidate the effectiveness of the treatment with honey. The time intervals in which the use of honey is effective is not clear. Furthermore, a physiological model is needed for in vitro testing, preferably mimicking peristalsis and dynamic flow of the applied substances. However, since it is easy to apply and of minimal risk in patients over one year of age, honey should be considered a possible treatment option during the interval between presentation and endoscopic removal of the retained BB. Systematic Review Registration: https://www.researchregistry.com/browse-the-registry#registryofsystematicreviewsmeta-analyses/registryofsystematicreviewsmeta-analysesdetails/643e9df96750410027ee11b0/, identifier: reviewregistry1581.

Assessment of the In Vivo Relationship Between Cerebral Hypometabolism, Tau Deposition, TSPO Expression, and Synaptic Density in a Tauopathy Mouse Model: a Multi-tracer PET Study.

Cerebral glucose hypometabolism is a typical hallmark of Alzheimer's disease (AD), usually associated with ongoing neurodegeneration and neuronal dysfunction. However, underlying pathological processes are not fully understood and reproducibility in animal models is not well established. The aim of the present study was to investigate the regional interrelation of glucose hypometabolism measured by [18F]FDG positron emission tomography (PET) with various molecular targets of AD pathophysiology using the PET tracers [18F]PI-2620 for tau deposition, [18F]DPA-714 for TSPO expression associated with neuroinflammation, and [18F]UCB-H for synaptic density in a transgenic tauopathy mouse model. Seven-month-old rTg4510 mice (n = 8) and non-transgenic littermates (n = 8) were examined in a small animal PET scanner with the tracers listed above. Hypometabolism was observed throughout the forebrain of rTg4510 mice. Tau pathology, increased TSPO expression, and synaptic loss were co-localized in the cortex and hippocampus and correlated with hypometabolism. In the thalamus, however, hypometabolism occurred in the absence of tau-related pathology. Thus, cerebral hypometabolism was associated with two regionally distinct forms of molecular pathology: (1) characteristic neuropathology of the Alzheimer-type including synaptic degeneration and neuroinflammation co-localized with tau deposition in the cerebral cortex, and (2) pathological changes in the thalamus in the absence of other markers of AD pathophysiology, possibly reflecting downstream or remote adaptive processes which may affect functional connectivity. Our study demonstrates the feasibility of a multitracer approach to explore complex interactions of distinct AD-pathomechanisms in vivo in a small animal model. The observations demonstrate that multiple, spatially heterogeneous pathomechanisms can contribute to hypometabolism observed in AD mouse models and they motivate future longitudinal studies as well as the investigation of possibly comparable pathomechanisms in human patients.

Prophylactic Drain Placement in Childhood Perforated Appendicitis: Does Spillage Matter?

Background: Prophylactic abdominal drains for perforated appendicitis in children have generally been regarded as obsolete because several studies showed inferior results for drain placement in the past. Despite these results, prophylactic abdominal drains for perforated appendicitis remain omnipresent in pediatric surgery especially when gross spillage is observed at the time of appendectomy. Here, we hypothesize that even if accounting for gross intra-abdominal spillage, prophylactic drain placement for perforated appendicitis in children is not beneficial. Patients and Methods: The charts of all children (<18 years) who underwent an appendectomy at our institution from July 2013 to March 2020 were analyzed. The data from 65 patients who presented with perforated appendicitis were included. Patients were grouped according to the amount of intraoperative spillage. Demographics, laboratory data, operative findings, and postoperative outcomes were analyzed. Results: Of all patients, 34 were male, and 31 were female, with a mean age of 10.5 ± 3.7 years. There were no statistically significant differences between the groups for age and sex (p = 0.6985 and p = 0.6222, respectively). Prophylactic drains were placed according to the surgeon's preference in 32 children. There were no statistically significant differences between the groups in the rate of intra-abdominal abscess formation, wound infection, and bowel obstruction, regardless of the amount of spillage encountered during an appendectomy. However, independently of the amount of spillage, the length of hospital stay was longer in the children in which a drain had been placed (p = 0.0041). Conclusion: In our cohort, we could not find a benefit from drain placement even in case of gross spillage at the time of appendectomy. Rather, drain placement was associated with an increase in length of hospital stay.