Deprescribing of antidepressants: development of indicators of high-risk and overprescribing using the RAND/UCLA Appropriateness Method.

BACKGROUND: Antidepressants are first-line medications for many psychiatric disorders. However, their widespread long-term use in some indications (e.g., mild depression and insomnia) is concerning. Particularly in older adults with comorbidities and polypharmacy, who are more susceptible to adverse drug reactions, the risks and benefits of treatment should be regularly reviewed. The aim of this consensus process was to identify explicit criteria of potentially inappropriate antidepressant use (indicators) in order to support primary care clinicians in identifying situations, where deprescribing of antidepressants should be considered. METHODS: We used the RAND/UCLA Appropriateness Method to identify the indicators of high-risk and overprescribing of antidepressants. We combined a structured literature review with a 3-round expert panel, with results discussed in moderated meetings in between rounds. Each of the 282 candidate indicators was scored on a 9-point Likert scale representing the necessity of a critical review of antidepressant continuation (1-3 = not necessary; 4-6 = uncertain; 7-9 = clearly necessary). Experts rated the indicators for the necessity of review, since decisions to deprescribe require considerations of patient risk/benefit balance and preferences. Indicators with a median necessity rating of ≥ 7 without disagreement after 3 rating rounds were accepted. RESULTS: The expert panel comprised 2 general practitioners, 2 clinical pharmacologists, 1 gerontopsychiatrist, 2 psychiatrists, and 3 internists/geriatricians (total N = 10). After 3 assessment rounds, there was consensus for 37 indicators of high-risk and 25 indicators of overprescribing, where critical reviews were felt to be necessary. High-risk prescribing indicators included settings posing risks of drug-drug, drug-disease, and drug-age interactions or the occurrence of adverse drug reactions. Indicators with the highest ratings included those suggesting the possibility of cardiovascular risks (QTc prolongation), delirium, gastrointestinal bleeding, and liver injury in specific patient subgroups with additional risk factors. Overprescribing indicators target patients with long treatment durations for depression, anxiety, and insomnia as well as high doses for pain and insomnia. CONCLUSIONS: Explicit indicators of antidepressant high-risk and overprescribing may be used directly by patients and health care providers, and integrated within clinical decision support tools, in order to improve the overall risk/benefit balance of this commonly prescribed class of prescription drugs.

Antidepressant nonadherence and sexual dysfunction among young adult males: the cross-sectional YAMAN study.

PURPOSE: Selective serotonin reuptake inhibitors are associated with high rates of nonadherence and sexual dysfunction, yet the correlation between these findings in young adult men is poorly characterized. We aimed to evaluate if young adult men are less willing to adhere to antidepressant treatment due to intolerable side effects, such as sexual dysfunction. METHODS: Deidentified, compensated survey that assessed baseline demographics, PHQ-8 and GAD-7 scores, attitudes towards antidepressant medication side effects, and perceptions of antidepressant medications including selective serotonin reuptake inhibitors, bupropion, and mirtazapine. RESULTS: From 665 delivered surveys, 505 respondents completed their survey (response rate: 76%), of which 486 were included for final analysis. After seeing common side effect profiles, our sample's willingness to take sexual function-sparing agents, such as bupropion or mirtazapine, was significantly greater than selective serotonin reuptake inhibitors (p < 0.001), with no significant difference between bupropion and mirtazapine (p = 0.263). The negative influence of erectile dysfunction and anorgasmia scored significantly higher than other common antidepressant side effects like weight gain, nausea, and dry mouth (range: p < 0.001, p = 0.043). With the exception of insomnia, participants indicated that experiencing sexual dysfunction while taking an antidepressant medication would lead to nonadherence at a significantly higher frequency than any other side effect assessed (range: p < 0.001, p = 0.005). CONCLUSION: The risk of experiencing sexual side effects when taking antidepressants could lead young adult men to become nonadherent to these medications. Strategies to augment the effectiveness of antidepressants, such as shared decision-making and the use of sexual function-sparing agents, are critical.

Suspected duloxetine-induced restless legs syndrome phenotypic variant: a case report.

BACKGROUND: Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects. CASE PRESENTATION: A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge. DISCUSSION AND CONCLUSIONS: This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.

Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy.

INTRODUCTION: We aimed to assess the effect of antidepressant use on dementia risk, cognitive decline, and brain atrophy. METHODS: In this prospective cohort study, we included 5511 dementia-free participants (Mini-Mental State Examination [MMSE] > 25) of the Rotterdam study (57.5% women, mean age 70.6 years). Antidepressant use was extracted from pharmacy records from 1991 until baseline (2002-2008). Incident dementia was monitored from baseline until 2018, with repeated cognitive assessment and magnetic resonance imaging (MRI) every 4 years. RESULTS: Compared to never use, any antidepressant use was not associated with dementia risk (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.92-1.41), or with accelerated cognitive decline or atrophy of white and gray matter. Compared to never use, dementia risk was somewhat higher with tricyclic antidepressants (HR 1.36, 95% CI 1.01-1.83) than with selective serotonin reuptake inhibitors (HR 1.12, 95% CI 0.81-1.54), but without dose-response relationships, accelerated cognitive decline, or atrophy in either group. DISCUSSION: Antidepressant medication in adults without indication of cognitive impairment was not consistently associated with long-term adverse cognitive effects. HIGHLIGHTS: Antidepressant medications are frequently prescribed, especially among older adults. In this study, antidepressant use was not associated with long-term dementia risk. Antidepressant use was not associated with cognitive decline or brain atrophy. Our results support safe prescription in an older, cognitively healthy population.

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice.

BACKGROUND AND PURPOSE: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. METHODS: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. RESULTS: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years±8.43 and H&Y stage was 3 [2-4]. Mean dose of levodopa used was 703.75mg±233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. CONCLUSIONS: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.

Validation of the predictive value of BDNF -87 methylation for antidepressant treatment success in severely depressed patients-a randomized rater-blinded trial.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is essential for antidepressant treatment of major depressive disorder (MDD). Our repeated studies suggest that DNA methylation of a specific CpG site in the promoter region of exon IV of the BDNF gene (CpG -87) might be predictive of the efficacy of monoaminergic antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others. This trial aims to evaluate whether knowing the biomarker is non-inferior to treatment-as-usual (TAU) regarding remission rates while exhibiting significantly fewer adverse events (AE). METHODS: The BDNF trial is a prospective, randomized, rater-blinded diagnostic study conducted at five university hospitals in Germany. The study's main hypothesis is that {1} knowing the methylation status of CpG -87 is non-inferior to not knowing it with respect to the remission rate while it significantly reduces the AE rate in patients experiencing at least one AE. The baseline assessment will occur upon hospitalization and a follow-up assessment on day 49 (± 3). A telephone follow-up will be conducted on day 70 (± 3). A total of 256 patients will be recruited, and methylation will be evaluated in all participants. They will be randomly assigned to either the marker or the TAU group. In the marker group, the methylation results will be shared with both the patient and their treating physician. In the TAU group, neither the patients nor their treating physicians will receive the marker status. The primary endpoints include the rate of patients achieving remission on day 49 (± 3), defined as a score of ≤ 10 on the Hamilton Depression Rating Scale (HDRS-24), and the occurrence of AE. ETHICS AND DISSEMINATION: The trial protocol has received approval from the Institutional Review Boards at the five participating universities. This trial holds significance in generating valuable data on a predictive biomarker for antidepressant treatment in patients with MDD. The findings will be shared with study participants, disseminated through professional society meetings, and published in peer-reviewed journals. TRIAL REGISTRATION: German Clinical Trial Register DRKS00032503. Registered on 17 August 2023.

Depression Treatment in Pregnancy: Is It Safe, or Is It Not?

Prenatal depression carries substantial risks for maternal and fetal health and increases susceptibility to postpartum depression. Untreated depression in pregnancy is correlated with adverse outcomes such as an increased risk of suicidal ideation, miscarriage and neonatal growth problems. Notwithstanding concerns about the use of antidepressants, the available treatment options emphasize the importance of specialized medical supervision during gestation. The purpose of this paper is to conduct a brief literature review on the main antidepressant drugs and their effects on pregnancy, assessing their risks and benefits. The analysis of the literature shows that it is essential that pregnancy be followed by specialized doctors and multidisciplinary teams (obstetricians, psychiatrists and psychologists) who attend to the woman's needs. Depression can now be treated safely during pregnancy by choosing drugs that have no teratogenic effects and fewer side effects for both mother and child. Comprehensive strategies involving increased awareness, early diagnosis, clear guidelines and effective treatment are essential to mitigate the impact of perinatal depression.

Role of adjunctive cariprazine for treatment-resistant depression in patients with major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD. Therefore, we aim to perform the first meta-analysis of current literature, to collate changes in depression from baseline and assess tolerability of adjunctive cariprazine in MDD populace. METHODS: PubMed, Embase, Google Scholar, ClinicalTrials.Gov, and Cochrane Library were searched from inception till 1st September 2023. RCTs of adult patients with refractory MDD under adjunctive cariprazine vs. placebo were included. Primary outcomes included improvement in MADRS, CGI-S, and HAM-D 17 scores. Secondary outcomes included treatment-emergent adverse events. The statistical analysis was performed using generic inverse variance with random-effects model. The overall risk ratios (RR) were calculated for dichotomous outcomes. RESULTS: A total of five RCTs were analysed, enrolling 2013 participants (cariprazine: 959 participants, Placebo: 1054). Supplementation of ADT with cariprazine demonstrated a significant improvement in MADRAS, CGI-S and HAMD-17 scores from baseline (LSMD: -1.88, 95% CI [-2.94, -0.83], p=0.0005), (LSMD: -0.18, 95% CI [-0.29, -0.07], p=0.002), and (LSMD: -0.96, 95% CI [-1.70, -0.21], p=0.01) respectively. Treatment with adjunctive cariprazine therapy demonstrated significantly increased incidence of akathisia, nausea, dizziness, fatigue, restlessness, somnolence, and tremors when compared with placebo. CONCLUSION: Our meta-analysis provides evidence supporting the efficacy of adjunctive cariprazine in patients with refractory MDD. However, it is essential to consider the safety profile of cariprazine, particularly the increased risk of adverse events. The vigilant monitoring and management of these side effects should be integrated into clinical practice to minimize discontinuation rates and optimize patient outcomes.

Emotional Blunting in Depression in the PREDDICT Clinical Trial: Inflammation-Stratified Augmentation of Vortioxetine With Celecoxib.

BACKGROUND: Emotional symptoms are recognized as a key feature in individuals with major depressive disorder. Previously, emotional blunting has been described both as a side effect of antidepressant treatment and as a symptom of depression. Little is known about the change of emotional blunting during antidepressant treatment. METHODS: The PREDDICT trial is a randomized, placebo-controlled, 6-week trial on the augmentation of vortioxetine with the anti-inflammatory agent celecoxib or placebo. Presently we report on exploratory secondary outcomes of changes in emotional blunting in depression assessed with the Oxford Depression Questionnaire (ODQ) total score and subscores from baseline to 8-week, 3-month, and 6-month follow-up assessments. RESULTS: In the whole group, there was a significant improvement in the ODQ total score and all subscores after 8 weeks. After stratification of participants into the treatment groups, the ODQ total score as well as subscores related to emotional blunting as a symptom of depression (reduction in positive emotions, not caring) improved between baseline and all follow-up time points in both treatment groups. Changes in subscores considered as a side effect of antidepressants (general reduction in emotions, emotional detachment) were inconclusive in both treatment groups. Overall, the placebo-augmented group showed slightly better results in changes of emotional blunting scores than the celecoxib group as did those with elevated inflammation at screening, regardless of treatment group. CONCLUSIONS: This analysis suggests favorable effects of vortioxetine on emotional blunting in both short- and long-term course. The beneficial impact of vortioxetine on emotional blunting was weaker in celecoxib-augmented patients compared with placebo, possibly due to pharmacokinetic interactions. Clinical Trials Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p.

Bidirectional associations between mental disorders, antidepressants and cardiovascular disease.

BACKGROUND: Mental disorders have a high comorbidity with cardiovascular disease (CVD), but the causality between them has not been fully appreciated. OBJECTIVE: This study aimed to systematically explore the bidirectional causality between the two broad categories of diseases. METHODS: We conducted Mendelian randomisation (MR) and multivariable MR (MVMR) analyses to evaluate potential causal links between 10 mental disorders, the use of antidepressants and 7 CVDs. FINDINGS: We discovered that major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD) and insomnia exhibit connections with elevated risks of two or more CVDs. Moreover, the use of antidepressants is linked to heightened risks of each CVD. Each distinct CVD is correlated with a greater probability of taking antidepressants. Our MVMR analysis demonstrated that the use of antidepressants is correlated with the elevation of respective risks across all cardiovascular conditions. This includes arrhythmias (OR: 1.28), atrial fibrillation (OR: 1.44), coronary artery disease (OR: 1.16), hypertension (OR: 1.16), heart failure (OR: 1.16), stroke (OR: 1.44) and entire CVD group (OR: 1.35). However, MDD itself was not linked to a heightened risk of any CVD. CONCLUSIONS: The findings of our study indicate that MDD, insomnia and ADHD may increase the risk of CVD. Our findings highlight the utilisation of antidepressants as an independent risk factor for CVD, thus explaining the influence of MDD on CVD through the mediating effects of antidepressants. CLINICAL IMPLICATIONS: When treating patients with antidepressants, it is necessary to take into consideration the potential beneficial and detrimental effects of antidepressants.

Oral prolonged-release ketamine in treatment-resistant depression - A double-blind randomized placebo-controlled multicentre trial of KET01, a novel ketamine formulation - Clinical and safety results.

INTRODUCTION: We investigated the antidepressant effects of a novel oral prolonged-release formulation of racemic ketamine (KET01) in patients suffering from treatment-resistant depression (TRD) as add-on therapy. MATERIAL AND METHODS: Patients were randomized to an additional 160 mg/day or 240 mg/day KET01 or placebo for 14 days. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to day 15. For treatment group comparisons, we used ANOVA with pairwise least squares mean difference tests in a mixed model repeated measures analysis. RESULTS: Twenty-seven patients completed the double-blind protocol before trial premature termination due to poor recruitment during the COVID-19 pandemic. Mean (SD) MADRS scores on day 15 were 23 (10.32) in placebo, 25 (8.28) with 160 mg/day and 17 (10.32) with 240 mg/day KET01. MADRS change was numerically larger but statistically non-significant in the 240 mg/day KET01 group vs placebo on day 7 (-5.67; p = 00.106) and day 15 was (difference: 4.99; p = 00.15). In exploratory analysis, baseline leukocyte count correlated with response to KET01 (p = 00.01). Distribution of adverse event rates were comparable between the treatment arms. Safety analysis did not identify increased risk of suicidality, dissociation, hear rate, systolic and diastolic blood pressure associated with trial treatment. DISCUSSION: Our results suggest that adjunctive oral administration of prolonged-release ketamine at a dose of 240 mg/day shows a positive, although statistically non-significant, trend towards antidepressant efficacy, however, the benefit could not be confirmed due to premature trial termination. Given its ease of use and low side effects, further trials are warranted to investigate this route of ketamine administration as a promising potential treatment of TRD.

The risk of acute infections in new users of antidepressants: An observational cohort study.

BACKGROUND: Preclinical studies suggested that drugs that functionally inhibit acid sphingomyelinase (FIASMA)may enhance immune cell longevity and potentially offer protection against infections. Many antidepressants have shown FIASMA activity. METHODS: We conducted a cohort study using primary-care data from the UK-based Clinical Practice Research Datalink (2000-2021). We assessed the association of composite diagnosed acute infections in new users of fluoxetine, sertraline, paroxetine, or venlafaxine aged 18-80 years compared to citalopram. We compared SARS-CoV-2 infections between groups in a secondary analysis. We estimated incidence rates (IR) and IR ratios (IRR) of acute infections in four pairwise comparisons using negative binomial regression. We applied propensity score (PS) fine stratification to control for confounding. RESULTS: In the PS-weighted cohorts, we included 353,138 fluoxetine, 222,463 sertraline, 69,963 paroxetine, 32,608 venlafaxine, and between 515,996 and 516,583 new citalopram users. PS-weighted IRs ranged between 76.8 acute infections /1000 person-years (py) (sertraline) and 98.9 infections/1000 py (citalopram). We observed PS-weighted IRRs around unity for paroxetine (0.97, 95 % CI, 0.95-1.00), fluoxetine (0.94, 95 % CI, 0.92-0.95), and venlafaxine (0.90, 95 % CI, 0.87-0.94) vs citalopram. Reduced IRR for sertraline vs citalopram (0.84, 95 % CI, 0.82-0.85), became null within subgroups by cohort entry date. In the analysis of SARS-CoV-2 infection, no statistically relevant risk reduction was seen. LIMITATIONS: Analysis not limited to patients with diagnosed depression, possible underestimation of infection incidence, and unclear FIASMA activity of citalopram. CONCLUSIONS: Fluoxetine, sertraline, paroxetine, and venlafaxine were not associated with a reduced risk of acute infection when compared with the presumably weak FIASMA citalopram.

Recurrence of exostosis as a result of medication-induced bruxism: case study.

Introduction: Alveolar oral exostosis is a common, benign condition routinely found in dentistry. Clinical problems associated with exostoses are the maintenance of oral hygiene as well as the fabrication of prosthodontic appliances. Over time, exostoses may contribute to irritation and periodontal disease. Case description: The patient in this case study had a recurrence of exostoses and was bothered by consistent and prominent pain. She reported being a bruxer; her bruxism was exacerbated due to attention-deficit hyperactivity disorder and antidepressant medications. Discussion: The etiology behind the recurrence of exostosis is discussed. The most evident etiology seems to be persistence of medication-induced bruxism, specifically awake bruxism. Conclusion: It is necessary to take a proper history to identify the cause of the recurrence of exostosis. Dental hygienists can contribute to a better understanding of and provide better treatment options for patients who have medication-induced bruxism.

Introduction: L'exostose buccale alvéolaire est une affection bénigne courante couramment observée en dentisterie. Les problèmes cliniques associés aux exostoses sont le maintien de l'hygiène buccale ainsi que la fabrication d'appareils prosthodontiques. Avec le temps, les exostoses peuvent causer de l'irritation et des maladies parodontales. Description de cas: Dans cette étude de cas, la patiente présente des exostoses récurrentes et est dérangée par une douleur constante et proéminente. Elle a déclaré souffrir de bruxisme exacerbé par la prise de médicaments antidépresseurs et contre le trouble déficitaire de l'attention avec hyperactivité. Discussion: L'étiologie derrière la récurrence de l'exostose est abordée. L'étiologie la plus évidente semble être la persistance du bruxisme induit par les médicaments, en particulier le bruxisme diurne. Conclusion: Il est nécessaire d'obtenir les antécédents médicaux appropriés pour identifier la cause de la récurrence de l'exostose. Les hygiénistes dentaires peuvent contribuer à une meilleure compréhension et offrir de meilleures options de traitement aux patients atteints de bruxisme induit par les médicaments.

VigiBase Pharmacovigilance Studies on Antidepressant-Related Adverse Reactions: A Scoping Review.

VigiBase, the World Health Organization's collaborative global pharmaco-vigilance database, provides storage for millions of adverse drug reaction (ADR) reports. Pharmacovigilance scientists use the database to detect signals, assess, and understand trends in ADRs so that potential harms can be communicated. A search for pharmacovigilance studies on psychotropic-related ADR reports published over the past 5 years in VigiBase identified the majority to be antipsychotic-related ADRs, and within the antipsychotic class, clozapine-related. The nine antidepressant-related ADR reports were reviewed in more detail and provide an example of how the science of pharmacovigilance identifies and communicates medication risks. [Journal of Psychosocial Nursing and Mental Health Services, 62(3), 7-10.].

What Is Perinatal Depression?

This JAMA Patient Page describes perinatal depression screening and diagnosis and available treatment options.

Psychedelic Therapy: A Primer for Primary Care Clinicians-Psilocybin.

BACKGROUND: The primary psychoactive drug in magic mushrooms, psilocybin, induces profound alterations in consciousness through the 5-HT2A receptor. This review consolidates current research findings to elucidate the pharmacology, safety profile, and clinical applications of psilocybin. AREAS OF UNCERTAINTY: Despite initial concerns that psilocybin could cause psychosis, contemporary research has demonstrated that psilocybin is generally safe. The most common adverse effects are nausea and headache, yet both tend to be transient. Serious adverse events can generally be avoided in controlled settings such as clinical trials. However, in the largest clinical trial to date, there were a total of 7 reported cases of suicidal ideation, up to 12 weeks after receiving a single 25 mg dose of psilocybin. That being said, all 7 cases did not respond to the treatment. Although selective serotonin reuptake inhibitors may blunt the hallucinogenic qualities of psilocybin, preliminary research suggests that they may enhance its antidepressant effects. THERAPEUTIC ADVANCES: In clinical trials, psilocybin has shown promise for treating major depressive disorder and treatment-resistant depression. Initial studies indicated that 42%-57% of patients underwent remission after psilocybin-assisted therapy, which suggests that psilocybin is more effective than existing antidepressant medications. Clinical data have also demonstrated that psilocybin can manage substance use disorders and end-of-life anxiety with clinical outcomes that are sustained for months and sometimes years after 1 or 2 doses. LIMITATIONS: However, larger Phase II trials with more than 100 depressed participants have shown a much smaller remission rate of 25%-29%, though these studies still observed that psilocybin causes a significant reduction in depressive symptoms. CONCLUSIONS: Aside from ketamine, psilocybin is the most clinically well-researched psychedelic drug, with trials that have enrolled hundreds of participants and multiple therapeutic applications. Phase III trials will determine whether psilocybin lives up to the promise that it showed in previous clinical trials.

Efficacy of intravenous ketamine and intranasal esketamine with dose escalation for Major depression: A systematic review and meta-analysis.

OBJECTIVE: Intravenous (IV) racemic ketamine and intranasal (IN) esketamine have demonstrated rapid antidepressant effects in treatment-resistant depression (TRD). This systematic review aims to evaluate the efficacy and safety of ketamine and esketamine at various dosages for depression. METHODS: We included randomized controlled trials (RCTs) with parallel group dose comparison of ketamine and esketamine for depression/TRD. Ovid Medline, Embase, PsycINFO, Scopus and Cochrane databases were searched. Standardized mean differences were calculated using Hedges'-g to complete random effects meta-analysis. The efficacy outcomes were changes in depression outcomes for IV ketamine and IN esketamine respectively. Safety was assessed by reported adverse effects. RESULTS: A random effects meta-analysis of studies (n = 12) showed efficacy in reducing depression symptoms with IV ketamine (Hedges'g = 1.52 [0.98-2.22], Z = 4.23, p < 0.001) and IN esketamine (Hedges' g = 0.31 [0.18-0.44], Z = 4.53, P < 0.001) compared to control/placebo. Treatment response was observed at IV ketamine doses ≤0.2 mg/kg, >0.2-0.5 mg/kg and > 0.5 mg/kg. Higher IV ketamine doses (>0.5 mg/kg) did not lead to greater treatment response. Esketamine doses of 56-84 mg were superior to 28 mg dose. LIMITATIONS: Overall quality of evidence was low and limited by small number of studies. Publication bias was high. CONCLUSIONS: This meta-analysis suggests that IV ketamine may be efficacious at doses as low as 0.2 mg/kg, with increasing dose response at 0.5 mg/kg, without demonstrable increased benefit at 1 mg/kg, based on a small number of studies. Efficacy for IN esketamine increases with doses above 28 mg with best response being found between 56 and 84 mg for reducing depressive symptoms.

La depresión como factor de riesgo de la demencia: fisiopatología y modelos preclínicos de estudio / Depression as a risk factor for dementia: Pathophysiology and preclinical study models

El aumento de la esperanza de vida ha llevado a un incremento en la incidencia de enfermedades crónicas como la demencia. Tratar los factores de riesgo de la demencia, como la depresión, podría reducir su incidencia. Sin embargo, el tratamiento con antidepresivos no ha sido eficaz en el manejo de este síntoma, lo que aumenta el riesgo de demencia en el futuro. Es fundamental investigar las causas y el tratamiento de la depresión, y el uso de modelos animales es importante en este sentido. Este estudio busca analizar la relación entre la depresión y el riesgo de desarrollar demencia, así como los modelos preclínicos más relevantes para estudiar la depresión en roedores. (AU)

The increase in life expectancy has led to a rise in the incidence of chronic diseases, such as dementia. Treating the risk factors of dementia, such as depression, could help reduce its occurrence. However, antidepressant treatment has not proven effective in managing this symptom, thereby increasing the risk of dementia in the future. It is essential to investigate the causes and treatment of depression, and in this regard, the use of animal models is of great significance. This study aims to analyze the evidence supporting the relationship between depression and the risk of developing dementia, while also providing an update on the most relevant preclinical models for studying depression in rodents. (AU)

Coprolalia y copropraxia inducida por bupropión en un paciente autista y con trastorno obsesivo compulsivo / Bupropion-induced coprolalia and copropraxia in autistic and obsessive compulsive disorder patient

Se presenta el caso de un varón de 41 años, ingresado desde los 26 en la unidad residencial y rehabilitadora con los diagnósticos de trastorno del espectro autista y trastorno obsesivo compulsivo, en tratamiento con fluvoxamina, valproico, topiramato, risperidona y clonazepam. Tras un periodo de estabilidad, aparece un cuadro compatible con un episodio depresivo mayor, que se decide tratar con bupropión, para incidir en los síntomas de apatía y lentitud psicomotriz. Se produce una recuperación rápida en 2 semanas, pero comienza a presentar copropraxia y coprolalia, que nunca antes había presentado. Se retira el bupropión y desaparece la coprolalia en 2 semanas, pero mantiene parte de estas conductas, por lo se pauta acetato de ciproterona para controlarlas, con mejoría en una semana. Tres meses después de la retirada del bupropión, alcanzó la eutimia y ya no presentó ninguna alteración conductual de temática sexual, coprolalia ni copropraxia. La literatura confirma otros casos de aparición de tics en pacientes tratados con antidepresivos para un cuadro depresivo y comorbilidad con trastorno obsesivo compulsivo, pero casi ninguno por el uso de bupropión o con coprolalia y copropraxia. (AU)

The case is presented of a 41-year-old male, admitted since age 26 to the Residential and Rehabilitation Unit with the diagnoses of autism spectrum disorder and obsessive-compulsive disorder, and under treatment with fluvoxamine, valproic, topiramate, risperidone and clonazepam. After a period of stability, a picture compatible with a major depressive episode appear, which is treated with bupropion, in order to affect the symptoms of apathy and psychomotor slowness. There is a rapid recovery in two weeks, but he begins to present copropraxia and coprolalia, which he had never presented before. Bupropion is withdrawn and coprolalia disappears in two weeks, but he maintained some of these behaviors, so cyproterone acetate is prescribed to control them, with improvement in one week. Three months after withdrawal of bupropion, he reaches euthymia and no longer presented any sexual behavioral alteration, coprolalia or copropraxia. The literature confirms other cases of appearance of tics in patients treated with antidepressants for a depressive picture and comorbidity with obsessive-compulsive disorder, but almost none by the use of bupropion or with coprolalia and copropraxia. (AU)